Roxanne Nelson, RN, BSN

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

An oncologist who says she was fired for whistleblower retaliation and gender discrimination has now filed a lawsuit against her former employer.

Anne Grand’Maison, MD, was employed at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., for 5 years and was the first medical oncologist specifically trained in sarcoma to join the center since it was founded more than 130 years ago.

The lawsuit, filed on Jan. 31, alleges that she was pushed out of her job after raising numerous concerns about egregious medical misconduct and lack of patient safety at the facility.

Roswell Park Cancer Center “denies these unfounded claims, and will vigorously defend itself in this matter,” the organization said in a statement issued to this news organization.

The 75-page complaint alleges that Dr. Grand’Maison observed unacceptable conduct and treatment of patients, including sarcoma pathology reports replete with diagnostic errors, physicians who were not well educated in the latest sarcoma research, and senior doctors refusing to seek out second opinions even in difficult cases.

All of these issues put patient safety and lives at serious risk, according to the lawsuit, and Dr. Grand’Maison raised her concerns internally and attempted to create the necessary changes.

Of specific concern to Dr. Grand’Maison was the competence of Carl Morrison, MD, DVM, Roswell Park’s lead sarcoma pathologist and chair of pathology, whom she had questioned on many occasions and voiced concerns about to other senior staff. But once she made it known that she had gathered up medical records to prove that he had made numerous specific misdiagnoses that led to mistreatments, Dr. Grand’Maison was forced out of her job and the hospital, she said.

“Roswell failed the cancer patients who entrusted their lives to the hospital by ignoring risks to their safety,” Dr. Grand’Maison said in an interview. “The heart of my practice as an oncologist is the well-being of my patients and that is why I could not stay silent.

“I hope that by coming forward, Roswell will be held accountable for putting lives at risk,” she said.
 

Not up to date with best practices

Before joining Roswell, Dr. Grand’Maison had worked at the University of Texas MD Anderson Cancer Center, which is the top cancer center in the nation, noted David E. Gottlieb, a partner at Wigdor, the law firm that is representing her.

MD Anderson has set the standard for sarcoma care, as they treat the highest volume of sarcoma cases of any hospital in North America and they have the best survival outcomes for sarcoma patients, he said in an interview.

“She was bringing this knowledge and background to Roswell Park,” Mr. Gottlieb said. “She felt that Dr. Morrison was not up to date with best practices as far as diagnosing and treating sarcoma, and she raised numerous issues.

“He was not open to being critiqued and even rejected her request to send something out for a second opinion,” Mr. Gottlieb said. “Second opinions are routine in medicine, and it’s the standard of care. We are dealing with a person’s life and it’s not a personal attack – you could be wrong, and getting another opinion can save a patient’s life.”

But Dr. Morrison has been at Roswell Park for many years, is a good friend of Roswell’s president and CEO Candace Johnson, PhD, and is part of the “old guard,” and “really at the top of the organization,” Mr. Gottlieb said  “Whereas Dr. Grand’Maison was relatively new, and her opinions were not popular.”

The complaint was filed against defendants Roswell Park Comprehensive Care Center; Health Research Inc. Roswell Park Division; Candace Johnson, PhD; Carl Morrison, MD, DVM; Renier Brentjens, MD, PhD, deputy director and chair of medicine; and two other senior physicians.
 

Denial of ‘unfounded claims’

In its statement, Roswell Park pointed out that it is one of few centers in the nation recognized by the Sarcoma Alliance as a hospital with specialized expertise and resources for patients with sarcoma. “Our physician experts not only adhere strictly to national best practices in the diagnosis and care of patients with sarcoma, they determine and disseminate the standards of appropriate medical care as lead authors of national guidelines,” the center stated.

“The facts demonstrate that Roswell Park is a richly diverse and inclusive organization committed to optimizing cancer care by incorporating the expertise of teams of specialists from many subspecialties and disciplines,” according to the statement.
 

Resistance and male egos

Dr. Grand’Maison has been a licensed physician for more than 30 years, and received her MD in 1988 after graduating from Sherbrooke University in Quebec. Over the next few decades she worked in clinical medicine and research, both in Canada and the United States. In 2014, she became certified in medical oncology and then secured a clinical and research fellowship focusing on sarcoma at MD Anderson.

Two years later, after completing her fellowship, she accepted a full-time position as an assistant professor of oncology in the department of medical oncology’s sarcoma division at Roswell Park. She became the first medical oncologist with a subspecialty in sarcoma, and also brought with her the advanced techniques and aggressive treatment that had been pioneered by MD Anderson, and which had never been used at Roswell Park, according to the complaint.

However, Dr. Grand’Maison said that she began to encounter some resistance from those more familiar with Roswell’s previous standard operating procedures. For example, her practice of seeing patients on days when chemotherapy was administered was viewed by some of the advanced practice clinicians as a lack of confidence in their abilities.

According to the complaint, Dr. Grand’Maison found the sarcoma tumor board at Roswell to be “male-dominated, ego-driven, fraught with defensiveness, and rife with a lack of collegiality almost from the very beginning,” which was very different from her experience at MD Anderson.

Less than 6 months after joining Roswell, she said that Dr. Morrison began treating her in a condescending manner at the tumor board meetings when she asked him questions pertaining to a diagnosis. She viewed his “physically intimidating and aggressive conduct toward her as sexist, and it was a pattern of conduct that would persist in the years that followed.” Dr. Grand’Maison observed that Dr. Morrison never behaved that way toward the men when discussing a case.

Over time, Dr. Grand’Maison made numerous and near endless efforts to raise her concerns about patient safety and gender discrimination at Roswell Park and had reached out to her supervisor and to others in upper management, the complaint alleges. All of this appeared to fall on completely deaf ears as hospital “politics” and doctor egos took precedence. Dr. Morrison continued to try to intimidate her into “silence” and block her attempts to refine diagnoses to ensure proper treatment, and several other senior physicians enabled his behavior and ignored the risk it posed to patient safety, the complaint alleges.  

“While she raised complaints about gender discrimination, the crux of her complaint was patient safety,” Mr. Gottlieb emphasized.

Another issue was that Dr. Grand’Maison never received the proper clinical support she repeatedly requested and that was urgently needed. Thus, her patients faced other elevated safety risks as a result of the underresourced sarcoma clinic, she said.
 

Fired or resigned?

Dr. Grand’Maison left Roswell Park Cancer center last May, and has not worked since.

Although Dr. Grand’Maison stated that she was fired in retaliation for raising serious concerns, Roswell Park insists that she voluntarily resigned. Dr. Grand’Maison acknowledged that she wrote an email in January 2022 to the clinical practice plan coordinator in which she mentioned that her husband was planning to relocate back to Canada and that her last date at Roswell Park would be May 1, 2022. The coordinator never responded to that email. In the interim, her husband, also a physician with privileges at Roswell Park, made it known that he was not moving to Canada.

Dr. Grand’Maison said that, as she had not resigned, and everyone knew her husband wasn’t moving, she did not follow up on that January 2022 email, and then forgot about it.

“That email was used as the basis to force her out,”said her lawyer, Mr. Gottlieb. “The day after she put together a summary and extensively documented serious patient safety concerns, she got an email that her resignation had been accepted.”

None of the standard protocols for resignation had been completed, either by human resources or by her supervisors, Mr. Gottlieb contended. “The law says that they can’t take adverse action against her for filing a complaint, so they fired her under the guise of a resignation,” he said.

Roswell Park refused to rescind Dr. Grand’Maison’s resignation, despite multiple attempts on her part. She even contacted the CEO and stated that her January 2022 email was being used a pretext to push her out in retaliation, but she received no response, only that the matter had been referred to someone else.

“I am speaking out because time and again female doctors are unable to deliver on the promise of their medical training because of discrimination,” said Dr. Grand’Maison. “Roswell dismissed my expertise and diminished my value. While I worry that coming forward may affect my career, I am taking that risk to make the path easier for the women who will come behind me.”

A version of this article first appeared on Medscape.com.

A novel four-drug chemotherapy regimen improved survival outcomes compared with standard therapy in patients with metastatic metastatic pancreatic ductal adenocarcinoma (mPDAC) in a global phase 3 trial dubbed NAPOLI-3.

Liposomal irinotecan (Onivyde) plus 5-fluorouracil/leucovorin and oxaliplatin (together known as NALIRIFOX) extended both overall and progression-free survival compared with gemcitabine plus nab-paclitaxel when used as first-line therapy in treatment-naive patients with mPDAC.

“These results support the NALIRIFOX regimen as a new regimen for the first-line treatment of patients with metastatic PDAC,” said lead study author Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles (UCLA) and codirector of the UCLA GI Oncology Program. “This study indicates that the more aggressive chemotherapy approach should be considered for those patients who are able to tolerate it.”

The findings were presented at the ASCO Gastrointestinal Cancers Symposium 2023.

Liposomal irinotecan administered with 5-fluorouracil/leucovorin has been approved in both the United States and Europe for patients with mPDAC who experience disease progression after treatment with gemcitabine-based therapy. This new trial investigated the approach as a first-line option.

It involved 770 patients who were randomly assigned to one of two treatment arms: NALIRIFOX (liposomal irinotecan 50 mg/m², 5-fluorouracil 2400 mg/m², leucovorin 400 mg/m², and oxaliplatin 60 mg/m²; days 1 and 15 of 28-day cycle) or gemcitabine 1,000 mg/m² plus nab-paclitaxel 125 mg/m² (days 1, 8, and 15 of 28-day cycle).

Most patients in both study arms were male (53.3% and 59.4% for liposomal irinotecan/NALIRIFOX recipient vs. the control group, respectively), had at least three metastatic sites (38.9% and 36.4%), had liver metastases (80.2% and 80.4%), and had their main tumor located outside the head of the pancreas (61.6% and 59.7%).

Most patients (65% in both arms) were treated outside of North America and East Asia.

“This is truly a global study, enrolling in over 20 countries, with a mix of both academic and community centers,” said Dr. Wainberg.

At a median follow-up of 16.1 months, 544 events had occurred.

“The study met its primary endpoint of overall survival by improving the median from 9.2 months with gemcitabine plus nab-paclitaxel to 11.1 months with NALIFIROX-treated group,” said Dr. Wainberg. “The hazard ratio was 0.84, with a P value of .04.”

Significant improvement was also observed in progression-free survival: 7.4 months for NALIFIROX vs. 5.6 months for gemcitabine plus nab-paclitaxel (hazard ratio, 0.69; P < .0001).

The overall response rate for liposomal irinotecan/NALIRIFOX vs. nab-paclitaxel/gemcitabine was 41.8% vs. 36.2%, and the complete response rate was 0.3% in both arms.

Dr. Wainberg noted that about half of the patients in both groups underwent subsequent anticancer therapy (50.5% vs. 54.4%); this included systemic treatments, surgery, and radiation therapy.

Grade 3/4 treatment-emergent adverse events reported in ≥ 10% of patients in both groups included diarrhea (20.3% vs. 4.5%), nausea (11.9% vs. 2.6%), hypokalemia (15.1% vs. 4.0%), anemia (10.5% vs. 17.4%), and neutropenia (14.1% vs. 24.5%).

“When one looks at the nuances in the patients and the toxicity profiles, we can see these two regimens have very different toxicity profiles,” Dr. Wainberg said. “There was also less peripheral neuropathy seen in the NALIRIFOX arm relative to the nab-paclitaxel/gemcitabine arm.”

The differences in the toxicity profiles were related to the mechanisms of action, Dr. Wainberg explained. “No new safety concerns with the NALIRIFOX regimen were identified.”
 

New reference regimen

Dr. Wainberg concluded that the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma. “Hopefully it’s something we can build off of in the future.”

Discussant for this paper, Laura Goff, MD, MSCI, associate professor of medicine and the executive medical director for the Cancer Patient Care Center at Vanderbilt Ingram Cancer Center, Nashville, Tenn., agreed.

For “fit patients, these results support the NALIRIFOX regimen as the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma,” she said.

“It is the new standard for fit patients,” she added.

She also agreed with the authors’ conclusion that NALIRIFOX demonstrated clinically meaningful and statistically significant improvements in overall and progression-free survival compared with nab-paclitaxel/gemcitabine.

“The safety profile of NALIRFOX was manageable and consistent with the treatment components,” she said. “Both regimens had high toxicity rates, but their toxicity profiles were different.”

Dr. Goff pointed out that high rates of toxicity were seen in both arms, “despite the reputation that gemcitabine/nab-paclitaxel is a significantly easier regimen to tolerate. I would argue that these data do not necessarily support that.”

The study was funded by Ipsen. Dr. Wainberg reported relationships with Amgen, Arcus Bioscience, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Daiichi Sankyo/Astra Zeneca, Ipsen, Lilly, Merck, Novartis, Pfizer, Plexxikon, PureTech, QED Therapeutics, Seattle Genetics. Dr. Goff reported relationships with Agios, ASLAN Pharmaceuticals, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics. Most of the other sudy authors had disclosures.

A version of this article first appeared on Medscape.com.

A novel four-drug chemotherapy regimen improved survival outcomes compared with standard therapy in patients with metastatic metastatic pancreatic ductal adenocarcinoma (mPDAC) in a global phase 3 trial dubbed NAPOLI-3.

Liposomal irinotecan (Onivyde) plus 5-fluorouracil/leucovorin and oxaliplatin (together known as NALIRIFOX) extended both overall and progression-free survival compared with gemcitabine plus nab-paclitaxel when used as first-line therapy in treatment-naive patients with mPDAC.

“These results support the NALIRIFOX regimen as a new regimen for the first-line treatment of patients with metastatic PDAC,” said lead study author Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles (UCLA) and codirector of the UCLA GI Oncology Program. “This study indicates that the more aggressive chemotherapy approach should be considered for those patients who are able to tolerate it.”

The findings were presented at the ASCO Gastrointestinal Cancers Symposium 2023.

Liposomal irinotecan administered with 5-fluorouracil/leucovorin has been approved in both the United States and Europe for patients with mPDAC who experience disease progression after treatment with gemcitabine-based therapy. This new trial investigated the approach as a first-line option.

It involved 770 patients who were randomly assigned to one of two treatment arms: NALIRIFOX (liposomal irinotecan 50 mg/m², 5-fluorouracil 2400 mg/m², leucovorin 400 mg/m², and oxaliplatin 60 mg/m²; days 1 and 15 of 28-day cycle) or gemcitabine 1,000 mg/m² plus nab-paclitaxel 125 mg/m² (days 1, 8, and 15 of 28-day cycle).

Most patients in both study arms were male (53.3% and 59.4% for liposomal irinotecan/NALIRIFOX recipient vs. the control group, respectively), had at least three metastatic sites (38.9% and 36.4%), had liver metastases (80.2% and 80.4%), and had their main tumor located outside the head of the pancreas (61.6% and 59.7%).

Most patients (65% in both arms) were treated outside of North America and East Asia.

“This is truly a global study, enrolling in over 20 countries, with a mix of both academic and community centers,” said Dr. Wainberg.

At a median follow-up of 16.1 months, 544 events had occurred.

“The study met its primary endpoint of overall survival by improving the median from 9.2 months with gemcitabine plus nab-paclitaxel to 11.1 months with NALIFIROX-treated group,” said Dr. Wainberg. “The hazard ratio was 0.84, with a P value of .04.”

Significant improvement was also observed in progression-free survival: 7.4 months for NALIFIROX vs. 5.6 months for gemcitabine plus nab-paclitaxel (hazard ratio, 0.69; P < .0001).

The overall response rate for liposomal irinotecan/NALIRIFOX vs. nab-paclitaxel/gemcitabine was 41.8% vs. 36.2%, and the complete response rate was 0.3% in both arms.

Dr. Wainberg noted that about half of the patients in both groups underwent subsequent anticancer therapy (50.5% vs. 54.4%); this included systemic treatments, surgery, and radiation therapy.

Grade 3/4 treatment-emergent adverse events reported in ≥ 10% of patients in both groups included diarrhea (20.3% vs. 4.5%), nausea (11.9% vs. 2.6%), hypokalemia (15.1% vs. 4.0%), anemia (10.5% vs. 17.4%), and neutropenia (14.1% vs. 24.5%).

“When one looks at the nuances in the patients and the toxicity profiles, we can see these two regimens have very different toxicity profiles,” Dr. Wainberg said. “There was also less peripheral neuropathy seen in the NALIRIFOX arm relative to the nab-paclitaxel/gemcitabine arm.”

The differences in the toxicity profiles were related to the mechanisms of action, Dr. Wainberg explained. “No new safety concerns with the NALIRIFOX regimen were identified.”
 

New reference regimen

Dr. Wainberg concluded that the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma. “Hopefully it’s something we can build off of in the future.”

Discussant for this paper, Laura Goff, MD, MSCI, associate professor of medicine and the executive medical director for the Cancer Patient Care Center at Vanderbilt Ingram Cancer Center, Nashville, Tenn., agreed.

For “fit patients, these results support the NALIRIFOX regimen as the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma,” she said.

“It is the new standard for fit patients,” she added.

She also agreed with the authors’ conclusion that NALIRIFOX demonstrated clinically meaningful and statistically significant improvements in overall and progression-free survival compared with nab-paclitaxel/gemcitabine.

“The safety profile of NALIRFOX was manageable and consistent with the treatment components,” she said. “Both regimens had high toxicity rates, but their toxicity profiles were different.”

Dr. Goff pointed out that high rates of toxicity were seen in both arms, “despite the reputation that gemcitabine/nab-paclitaxel is a significantly easier regimen to tolerate. I would argue that these data do not necessarily support that.”

The study was funded by Ipsen. Dr. Wainberg reported relationships with Amgen, Arcus Bioscience, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Daiichi Sankyo/Astra Zeneca, Ipsen, Lilly, Merck, Novartis, Pfizer, Plexxikon, PureTech, QED Therapeutics, Seattle Genetics. Dr. Goff reported relationships with Agios, ASLAN Pharmaceuticals, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics. Most of the other sudy authors had disclosures.

A version of this article first appeared on Medscape.com.

A novel four-drug chemotherapy regimen improved survival outcomes compared with standard therapy in patients with metastatic metastatic pancreatic ductal adenocarcinoma (mPDAC) in a global phase 3 trial dubbed NAPOLI-3.

Liposomal irinotecan (Onivyde) plus 5-fluorouracil/leucovorin and oxaliplatin (together known as NALIRIFOX) extended both overall and progression-free survival compared with gemcitabine plus nab-paclitaxel when used as first-line therapy in treatment-naive patients with mPDAC.

“These results support the NALIRIFOX regimen as a new regimen for the first-line treatment of patients with metastatic PDAC,” said lead study author Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles (UCLA) and codirector of the UCLA GI Oncology Program. “This study indicates that the more aggressive chemotherapy approach should be considered for those patients who are able to tolerate it.”

The findings were presented at the ASCO Gastrointestinal Cancers Symposium 2023.

Liposomal irinotecan administered with 5-fluorouracil/leucovorin has been approved in both the United States and Europe for patients with mPDAC who experience disease progression after treatment with gemcitabine-based therapy. This new trial investigated the approach as a first-line option.

It involved 770 patients who were randomly assigned to one of two treatment arms: NALIRIFOX (liposomal irinotecan 50 mg/m², 5-fluorouracil 2400 mg/m², leucovorin 400 mg/m², and oxaliplatin 60 mg/m²; days 1 and 15 of 28-day cycle) or gemcitabine 1,000 mg/m² plus nab-paclitaxel 125 mg/m² (days 1, 8, and 15 of 28-day cycle).

Most patients in both study arms were male (53.3% and 59.4% for liposomal irinotecan/NALIRIFOX recipient vs. the control group, respectively), had at least three metastatic sites (38.9% and 36.4%), had liver metastases (80.2% and 80.4%), and had their main tumor located outside the head of the pancreas (61.6% and 59.7%).

Most patients (65% in both arms) were treated outside of North America and East Asia.

“This is truly a global study, enrolling in over 20 countries, with a mix of both academic and community centers,” said Dr. Wainberg.

At a median follow-up of 16.1 months, 544 events had occurred.

“The study met its primary endpoint of overall survival by improving the median from 9.2 months with gemcitabine plus nab-paclitaxel to 11.1 months with NALIFIROX-treated group,” said Dr. Wainberg. “The hazard ratio was 0.84, with a P value of .04.”

Significant improvement was also observed in progression-free survival: 7.4 months for NALIFIROX vs. 5.6 months for gemcitabine plus nab-paclitaxel (hazard ratio, 0.69; P < .0001).

The overall response rate for liposomal irinotecan/NALIRIFOX vs. nab-paclitaxel/gemcitabine was 41.8% vs. 36.2%, and the complete response rate was 0.3% in both arms.

Dr. Wainberg noted that about half of the patients in both groups underwent subsequent anticancer therapy (50.5% vs. 54.4%); this included systemic treatments, surgery, and radiation therapy.

Grade 3/4 treatment-emergent adverse events reported in ≥ 10% of patients in both groups included diarrhea (20.3% vs. 4.5%), nausea (11.9% vs. 2.6%), hypokalemia (15.1% vs. 4.0%), anemia (10.5% vs. 17.4%), and neutropenia (14.1% vs. 24.5%).

“When one looks at the nuances in the patients and the toxicity profiles, we can see these two regimens have very different toxicity profiles,” Dr. Wainberg said. “There was also less peripheral neuropathy seen in the NALIRIFOX arm relative to the nab-paclitaxel/gemcitabine arm.”

The differences in the toxicity profiles were related to the mechanisms of action, Dr. Wainberg explained. “No new safety concerns with the NALIRIFOX regimen were identified.”
 

New reference regimen

Dr. Wainberg concluded that the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma. “Hopefully it’s something we can build off of in the future.”

Discussant for this paper, Laura Goff, MD, MSCI, associate professor of medicine and the executive medical director for the Cancer Patient Care Center at Vanderbilt Ingram Cancer Center, Nashville, Tenn., agreed.

For “fit patients, these results support the NALIRIFOX regimen as the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma,” she said.

“It is the new standard for fit patients,” she added.

She also agreed with the authors’ conclusion that NALIRIFOX demonstrated clinically meaningful and statistically significant improvements in overall and progression-free survival compared with nab-paclitaxel/gemcitabine.

“The safety profile of NALIRFOX was manageable and consistent with the treatment components,” she said. “Both regimens had high toxicity rates, but their toxicity profiles were different.”

Dr. Goff pointed out that high rates of toxicity were seen in both arms, “despite the reputation that gemcitabine/nab-paclitaxel is a significantly easier regimen to tolerate. I would argue that these data do not necessarily support that.”

The study was funded by Ipsen. Dr. Wainberg reported relationships with Amgen, Arcus Bioscience, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Daiichi Sankyo/Astra Zeneca, Ipsen, Lilly, Merck, Novartis, Pfizer, Plexxikon, PureTech, QED Therapeutics, Seattle Genetics. Dr. Goff reported relationships with Agios, ASLAN Pharmaceuticals, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics. Most of the other sudy authors had disclosures.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m² twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m² twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m² twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding stereotactic body radiation therapy (SBRT) to sorafenib produced better outcomes among patients with hepatocellular carcinoma (HCC) than sorafenib alone, according to new findings.

The use of SBRT in this setting improved both overall survival and progression-free survival (PFS). There was no increase in adverse events with the addition of SBRT, and results trended toward a quality-of-life benefit at 6 months.

“This adds to the body of evidence for the role of external-beam radiation, bringing SBRT to the armamentarium of treatment options for patients – particularly those with locally advanced HCC and macrovascular invasion, especially if they are treated with tyrosine kinase inhibitors [TKIs],” said lead study author Laura A. Dawson, MD, a clinician scientist at the Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto.

Dr. Dawson presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Approached for an outside comment, Mary Feng, MD, professor of radiation oncology at the University of California, San Francisco, said, “This study is really groundbreaking.”

She added that the investigators should be congratulated for executing this ambitious study with worldwide enrollment for a serious disease.

“There are very few studies demonstrating an overall survival benefit from radiation or any local control modality,” she told this news organization. She suggested that the survival benefit seen in this trial was “likely due to the high percentage of patients (74%) with macrovascular invasion, who stand to benefit the most from treatment.

“This study has established the standard of adding SBRT to patients who are treated with TKIs and raises the question of whether adding SBRT to immunotherapy would also result in a survival benefit. This next question must also be tested in a prospective clinical trial,” she said.
 

Study details

At the study’s inception, sorafenib was the standard of care for patients who were unable to undergo surgery, ablation, and/or transarterial chemoembolization (TACE). Dr. Dawson explained that sorafenib had been shown to improve median overall survival, although there was less benefit if macrovascular invasion was present.

“Integrating radiation strategies in HCC management has been a key question over the past few decades,” she said.

In the current study, Dr. Dawson and colleagues added SBRT to sorafenib. The cohort included 177 patients with new or recurrent HCC who were not candidates for surgery, ablation, or TACE. They were randomly assigned to receive either sorafenib 400 mg twice daily or to SBRT (27.5-50 Gy in five fractions) followed by sorafenib 200 mg twice daily; the dosage was then increased to 400 mg twice daily after 28 days.
 

SBRT improves outcomes

The original plan was to enroll 292 participants, but accrual closed early when the standard of care for systemic treatment of HCC changed following the results of the phase 3 IMbrave150 trial, which showed the superiority of atezolizumab plus bevacizumab as frontline therapy for locally advanced or metastatic HCC. The closure of accrual was agreed upon by the investigators and the data safety monitoring committee, and their statistical analysis plan was revised accordingly. The study became time driven rather than event driven, she noted. This resulted in a decrease from 80% power to 65% power.

The median age of participants was 66 years (range, 27-84 years); 41% had hepatitis C, and 19% had hepatitis B or B/C. Additionally, 82% had Barcelona Clinic Liver Cancer stage C disease, and 74% had macrovascular invasion.

The median follow-up was 13.2 months overall and 33.7 months for living patients.

Median overall survival improved from 12.3 months with sorafenib alone to 15.8 months with the addition of SBRT to the regimen (hazard ratio [HR] = 0.77; one-sided P = .0554). A prespecified multivariable analysis showed that the combination therapy resulted in a statistically significant improvement in overall survival after adjustment for confounders (HR, 0.72; P = .042).

Similarly, median PFS also improved from 5.5 months with sorafenib alone to 9.2 months with SBRT and sorafenib (HR = 0.55; two-sided P = .0001).

With regard to safety, gastrointestinal bleeds occurred in 4% of patients in the combination arm, vs. 6% of those in the monotherapy arm. Overall, rates of treatment-related grade 3+ adverse events did not significantly differ between study arms (42% vs. 47%; P = .52). There were three grade 5 events; two in the sorafenib-only group and one in the SBRT/sorafenib group.

The researchers also evaluated quality of life (QoL). “Our hypothesis was that patients treated with SBRT and sorafenib would have improved quality of life 6 months after the start of treatment compared to sorafenib alone,” said Dr. Dawson.

About half (47%) of participants agreed to fill out QoL assessments, but baseline and 6-month data were available for only about 21% of participants. Although the numbers were considered too small to analyze statistically, substantial improvement was seen in the group that received combination therapy. A total of 10% of patients who received sorafenib reported improvement on the FACT-Hep score, vs. 35% of patients who received SBRT/sorafenib.

“As compared to sorafenib, SBRT improved overall survival and progression-free survival, with no observed increase in adverse events in patients with advanced HCC,” concluded Dr. Dawson.
 

Where does radiation fit?

Invited discussant Laura Goff, MD, associate professor of medicine, Vanderbilt Ingram Cancer Center, Nashville, Tenn., reiterated that SBRT given prior to sorafenib improved outcomes compared to sorafenib alone, and while not definitive, Quality and Outcomes Framework scores appeared to improve at 6 months for the combination arm. “This reassures our concerns about toxicity,” she said.

Dr. Goff pointed out that since the study closed early, owing to changes in standard of care for HCC, the question arises – where does radiation fit in the array of options now available for HCC?

“For one, sorafenib plus SBRT represents an intriguing first-line option for patients who cannot be treated with immunotherapy, such as those who experience a posttransplant recurrence,” Dr. Goff said. “There is also renewed interest in radiation therapy in liver-dominant HCC, and there is active investigation ongoing for a variety of combinations.”

Dr. Dawson reported relationships with Merck and Raysearch. Dr. Goff reported relationships with Agios, ASLAN, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding stereotactic body radiation therapy (SBRT) to sorafenib produced better outcomes among patients with hepatocellular carcinoma (HCC) than sorafenib alone, according to new findings.

The use of SBRT in this setting improved both overall survival and progression-free survival (PFS). There was no increase in adverse events with the addition of SBRT, and results trended toward a quality-of-life benefit at 6 months.

“This adds to the body of evidence for the role of external-beam radiation, bringing SBRT to the armamentarium of treatment options for patients – particularly those with locally advanced HCC and macrovascular invasion, especially if they are treated with tyrosine kinase inhibitors [TKIs],” said lead study author Laura A. Dawson, MD, a clinician scientist at the Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto.

Dr. Dawson presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Approached for an outside comment, Mary Feng, MD, professor of radiation oncology at the University of California, San Francisco, said, “This study is really groundbreaking.”

She added that the investigators should be congratulated for executing this ambitious study with worldwide enrollment for a serious disease.

“There are very few studies demonstrating an overall survival benefit from radiation or any local control modality,” she told this news organization. She suggested that the survival benefit seen in this trial was “likely due to the high percentage of patients (74%) with macrovascular invasion, who stand to benefit the most from treatment.

“This study has established the standard of adding SBRT to patients who are treated with TKIs and raises the question of whether adding SBRT to immunotherapy would also result in a survival benefit. This next question must also be tested in a prospective clinical trial,” she said.
 

Study details

At the study’s inception, sorafenib was the standard of care for patients who were unable to undergo surgery, ablation, and/or transarterial chemoembolization (TACE). Dr. Dawson explained that sorafenib had been shown to improve median overall survival, although there was less benefit if macrovascular invasion was present.

“Integrating radiation strategies in HCC management has been a key question over the past few decades,” she said.

In the current study, Dr. Dawson and colleagues added SBRT to sorafenib. The cohort included 177 patients with new or recurrent HCC who were not candidates for surgery, ablation, or TACE. They were randomly assigned to receive either sorafenib 400 mg twice daily or to SBRT (27.5-50 Gy in five fractions) followed by sorafenib 200 mg twice daily; the dosage was then increased to 400 mg twice daily after 28 days.
 

SBRT improves outcomes

The original plan was to enroll 292 participants, but accrual closed early when the standard of care for systemic treatment of HCC changed following the results of the phase 3 IMbrave150 trial, which showed the superiority of atezolizumab plus bevacizumab as frontline therapy for locally advanced or metastatic HCC. The closure of accrual was agreed upon by the investigators and the data safety monitoring committee, and their statistical analysis plan was revised accordingly. The study became time driven rather than event driven, she noted. This resulted in a decrease from 80% power to 65% power.

The median age of participants was 66 years (range, 27-84 years); 41% had hepatitis C, and 19% had hepatitis B or B/C. Additionally, 82% had Barcelona Clinic Liver Cancer stage C disease, and 74% had macrovascular invasion.

The median follow-up was 13.2 months overall and 33.7 months for living patients.

Median overall survival improved from 12.3 months with sorafenib alone to 15.8 months with the addition of SBRT to the regimen (hazard ratio [HR] = 0.77; one-sided P = .0554). A prespecified multivariable analysis showed that the combination therapy resulted in a statistically significant improvement in overall survival after adjustment for confounders (HR, 0.72; P = .042).

Similarly, median PFS also improved from 5.5 months with sorafenib alone to 9.2 months with SBRT and sorafenib (HR = 0.55; two-sided P = .0001).

With regard to safety, gastrointestinal bleeds occurred in 4% of patients in the combination arm, vs. 6% of those in the monotherapy arm. Overall, rates of treatment-related grade 3+ adverse events did not significantly differ between study arms (42% vs. 47%; P = .52). There were three grade 5 events; two in the sorafenib-only group and one in the SBRT/sorafenib group.

The researchers also evaluated quality of life (QoL). “Our hypothesis was that patients treated with SBRT and sorafenib would have improved quality of life 6 months after the start of treatment compared to sorafenib alone,” said Dr. Dawson.

About half (47%) of participants agreed to fill out QoL assessments, but baseline and 6-month data were available for only about 21% of participants. Although the numbers were considered too small to analyze statistically, substantial improvement was seen in the group that received combination therapy. A total of 10% of patients who received sorafenib reported improvement on the FACT-Hep score, vs. 35% of patients who received SBRT/sorafenib.

“As compared to sorafenib, SBRT improved overall survival and progression-free survival, with no observed increase in adverse events in patients with advanced HCC,” concluded Dr. Dawson.
 

Where does radiation fit?

Invited discussant Laura Goff, MD, associate professor of medicine, Vanderbilt Ingram Cancer Center, Nashville, Tenn., reiterated that SBRT given prior to sorafenib improved outcomes compared to sorafenib alone, and while not definitive, Quality and Outcomes Framework scores appeared to improve at 6 months for the combination arm. “This reassures our concerns about toxicity,” she said.

Dr. Goff pointed out that since the study closed early, owing to changes in standard of care for HCC, the question arises – where does radiation fit in the array of options now available for HCC?

“For one, sorafenib plus SBRT represents an intriguing first-line option for patients who cannot be treated with immunotherapy, such as those who experience a posttransplant recurrence,” Dr. Goff said. “There is also renewed interest in radiation therapy in liver-dominant HCC, and there is active investigation ongoing for a variety of combinations.”

Dr. Dawson reported relationships with Merck and Raysearch. Dr. Goff reported relationships with Agios, ASLAN, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding stereotactic body radiation therapy (SBRT) to sorafenib produced better outcomes among patients with hepatocellular carcinoma (HCC) than sorafenib alone, according to new findings.

The use of SBRT in this setting improved both overall survival and progression-free survival (PFS). There was no increase in adverse events with the addition of SBRT, and results trended toward a quality-of-life benefit at 6 months.

“This adds to the body of evidence for the role of external-beam radiation, bringing SBRT to the armamentarium of treatment options for patients – particularly those with locally advanced HCC and macrovascular invasion, especially if they are treated with tyrosine kinase inhibitors [TKIs],” said lead study author Laura A. Dawson, MD, a clinician scientist at the Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto.

Dr. Dawson presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Approached for an outside comment, Mary Feng, MD, professor of radiation oncology at the University of California, San Francisco, said, “This study is really groundbreaking.”

She added that the investigators should be congratulated for executing this ambitious study with worldwide enrollment for a serious disease.

“There are very few studies demonstrating an overall survival benefit from radiation or any local control modality,” she told this news organization. She suggested that the survival benefit seen in this trial was “likely due to the high percentage of patients (74%) with macrovascular invasion, who stand to benefit the most from treatment.

“This study has established the standard of adding SBRT to patients who are treated with TKIs and raises the question of whether adding SBRT to immunotherapy would also result in a survival benefit. This next question must also be tested in a prospective clinical trial,” she said.
 

Study details

At the study’s inception, sorafenib was the standard of care for patients who were unable to undergo surgery, ablation, and/or transarterial chemoembolization (TACE). Dr. Dawson explained that sorafenib had been shown to improve median overall survival, although there was less benefit if macrovascular invasion was present.

“Integrating radiation strategies in HCC management has been a key question over the past few decades,” she said.

In the current study, Dr. Dawson and colleagues added SBRT to sorafenib. The cohort included 177 patients with new or recurrent HCC who were not candidates for surgery, ablation, or TACE. They were randomly assigned to receive either sorafenib 400 mg twice daily or to SBRT (27.5-50 Gy in five fractions) followed by sorafenib 200 mg twice daily; the dosage was then increased to 400 mg twice daily after 28 days.
 

SBRT improves outcomes

The original plan was to enroll 292 participants, but accrual closed early when the standard of care for systemic treatment of HCC changed following the results of the phase 3 IMbrave150 trial, which showed the superiority of atezolizumab plus bevacizumab as frontline therapy for locally advanced or metastatic HCC. The closure of accrual was agreed upon by the investigators and the data safety monitoring committee, and their statistical analysis plan was revised accordingly. The study became time driven rather than event driven, she noted. This resulted in a decrease from 80% power to 65% power.

The median age of participants was 66 years (range, 27-84 years); 41% had hepatitis C, and 19% had hepatitis B or B/C. Additionally, 82% had Barcelona Clinic Liver Cancer stage C disease, and 74% had macrovascular invasion.

The median follow-up was 13.2 months overall and 33.7 months for living patients.

Median overall survival improved from 12.3 months with sorafenib alone to 15.8 months with the addition of SBRT to the regimen (hazard ratio [HR] = 0.77; one-sided P = .0554). A prespecified multivariable analysis showed that the combination therapy resulted in a statistically significant improvement in overall survival after adjustment for confounders (HR, 0.72; P = .042).

Similarly, median PFS also improved from 5.5 months with sorafenib alone to 9.2 months with SBRT and sorafenib (HR = 0.55; two-sided P = .0001).

With regard to safety, gastrointestinal bleeds occurred in 4% of patients in the combination arm, vs. 6% of those in the monotherapy arm. Overall, rates of treatment-related grade 3+ adverse events did not significantly differ between study arms (42% vs. 47%; P = .52). There were three grade 5 events; two in the sorafenib-only group and one in the SBRT/sorafenib group.

The researchers also evaluated quality of life (QoL). “Our hypothesis was that patients treated with SBRT and sorafenib would have improved quality of life 6 months after the start of treatment compared to sorafenib alone,” said Dr. Dawson.

About half (47%) of participants agreed to fill out QoL assessments, but baseline and 6-month data were available for only about 21% of participants. Although the numbers were considered too small to analyze statistically, substantial improvement was seen in the group that received combination therapy. A total of 10% of patients who received sorafenib reported improvement on the FACT-Hep score, vs. 35% of patients who received SBRT/sorafenib.

“As compared to sorafenib, SBRT improved overall survival and progression-free survival, with no observed increase in adverse events in patients with advanced HCC,” concluded Dr. Dawson.
 

Where does radiation fit?

Invited discussant Laura Goff, MD, associate professor of medicine, Vanderbilt Ingram Cancer Center, Nashville, Tenn., reiterated that SBRT given prior to sorafenib improved outcomes compared to sorafenib alone, and while not definitive, Quality and Outcomes Framework scores appeared to improve at 6 months for the combination arm. “This reassures our concerns about toxicity,” she said.

Dr. Goff pointed out that since the study closed early, owing to changes in standard of care for HCC, the question arises – where does radiation fit in the array of options now available for HCC?

“For one, sorafenib plus SBRT represents an intriguing first-line option for patients who cannot be treated with immunotherapy, such as those who experience a posttransplant recurrence,” Dr. Goff said. “There is also renewed interest in radiation therapy in liver-dominant HCC, and there is active investigation ongoing for a variety of combinations.”

Dr. Dawson reported relationships with Merck and Raysearch. Dr. Goff reported relationships with Agios, ASLAN, AstraZeneca, Basilea, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Genentech, Merck, and QED Therapeutics.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Patients with refractory advanced gastroesophageal cancer (AGOC) have a poor prognosis, with limited options following failure of second-line therapy. New data showing improved survival suggest that regorafenib (Stivarga) may offer a new treatment option in these patients.

“Regorafenib significantly improves survival compared with placebo in patients with refractory AGOC, delaying deterioration in global quality of life,” said lead author Nick Pavlakis, PhD, MBBS, Royal North Shore Hospital, St. Leonards, Australia. “There were also no new toxicity signals.”

He emphasized that benefit was consistent in all preplanned subgroups. “This offers a new treatment option in this setting,” Dr. Pavlakis said.

He presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Regorafenib is an oral multikinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-beta, FGFR), and oncogenesis (RAF, RET, and KIT). It is already approved for several indications including metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma. 

AGOC could be a new indication for the drug. Use in this patient population was explored in an earlier trial, Dr. Pavlakis commented.

“We previously demonstrated the regorafenib prolonged progression-free survival in the INTEGRATE phase 2 trial,” he said. “Based on those results, we undertook the phase 3 INTEGRATE II study. The goal was to examine if regorafenib improves overall survival after failure of at least two lines of treatment.”

However, Dr. Pavlakis noted that during the conduct of this study, there was a change of practice in gastric cancer. “There was an evolution of new evidence in support of additional chemotherapy and immune checkpoint inhibitors such as nivolumab, and very interesting data on the combination of nivolumab and regorafenib from a study being conducted in Japan. So we amended the protocol and evolved the INTEGRATE II to INTEGRATE IIa, to continue evaluating regorafenib versus placebo, and then to evolve to the INTEGRATE IIb study to evaluate regorafenib plus nivolumab versus chemotherapy,” he explained.

The results he presented at the meeting came from the phase 3 INTEGRATE II part of this trial. The other part of the trial, INTEGRATE IIb, is still accruing.

A total of 251 patients were enrolled from five countries and stratified by tumor location, geographic location (Asia vs. “rest of the world”), and prior treatment with VEGF inhibitors.

The cohort was randomly assigned to receive 160 mg regorafenib and best supportive care or placebo plus BSC.

After 238 events, the overall survival hazard ratio was 0.68. “The survival benefit of regorafenib was best observed in the 12-month survival of 19% versus 6%,” said Pavlakis.

The median overall survival for regorafenib versus placebo was 4.5 versus 4.0 months (HR, 0.70; P = .011).

After preplanned adjustment for multiplicity, there were no statistically significant differences across regions (Asia vs. non-Asia) or other prespecified subgroups.

In the pooled analysis, which included study populations from both the INTEGRATE and INTEGRATE IIa populations, the median overall survival was 5.0 versus 4.1 (HR, 0.70; P = .001).  

Regorafenib also improved progression-free survival (median PFS, 1.8 vs. 1.6 months; HR, 0.52; P < .0001) and it delayed deterioration in global quality of life as compared with placebo (P = .0043).

Toxicity was similar to that previously reported in other studies, and adverse events were mostly grade 1 and 2.
 

A building block?

In a comment, Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Conn., said that she would consider the results with regorafenib in this setting as statistically significant, but with questionable clinical significance.

“The median overall survival difference 0.5 months or about 2 weeks is very modest, especially when taking into consideration the side effect profile,” she said. “I think that regorafenib as a building block for the additional phase 3 study is more interesting.”

“There is data that suggests synergy between VEGF inhibitors and immune checkpoint inhibitors, so I am eager to see the results of INEGRATE IIb [exploring regorafenib use with nivolumab],” Dr. Kunz added.

The study is sponsored by the Australasian Gastro-Intestinal Trials Group. Dr. Pavlakis reported relationships with Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Kunz reported relationships with Ipsen, Novartis (Advanced Accelerator Applications), Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and Isotope Technologies Munich.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Patients with refractory advanced gastroesophageal cancer (AGOC) have a poor prognosis, with limited options following failure of second-line therapy. New data showing improved survival suggest that regorafenib (Stivarga) may offer a new treatment option in these patients.

“Regorafenib significantly improves survival compared with placebo in patients with refractory AGOC, delaying deterioration in global quality of life,” said lead author Nick Pavlakis, PhD, MBBS, Royal North Shore Hospital, St. Leonards, Australia. “There were also no new toxicity signals.”

He emphasized that benefit was consistent in all preplanned subgroups. “This offers a new treatment option in this setting,” Dr. Pavlakis said.

He presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Regorafenib is an oral multikinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-beta, FGFR), and oncogenesis (RAF, RET, and KIT). It is already approved for several indications including metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma. 

AGOC could be a new indication for the drug. Use in this patient population was explored in an earlier trial, Dr. Pavlakis commented.

“We previously demonstrated the regorafenib prolonged progression-free survival in the INTEGRATE phase 2 trial,” he said. “Based on those results, we undertook the phase 3 INTEGRATE II study. The goal was to examine if regorafenib improves overall survival after failure of at least two lines of treatment.”

However, Dr. Pavlakis noted that during the conduct of this study, there was a change of practice in gastric cancer. “There was an evolution of new evidence in support of additional chemotherapy and immune checkpoint inhibitors such as nivolumab, and very interesting data on the combination of nivolumab and regorafenib from a study being conducted in Japan. So we amended the protocol and evolved the INTEGRATE II to INTEGRATE IIa, to continue evaluating regorafenib versus placebo, and then to evolve to the INTEGRATE IIb study to evaluate regorafenib plus nivolumab versus chemotherapy,” he explained.

The results he presented at the meeting came from the phase 3 INTEGRATE II part of this trial. The other part of the trial, INTEGRATE IIb, is still accruing.

A total of 251 patients were enrolled from five countries and stratified by tumor location, geographic location (Asia vs. “rest of the world”), and prior treatment with VEGF inhibitors.

The cohort was randomly assigned to receive 160 mg regorafenib and best supportive care or placebo plus BSC.

After 238 events, the overall survival hazard ratio was 0.68. “The survival benefit of regorafenib was best observed in the 12-month survival of 19% versus 6%,” said Pavlakis.

The median overall survival for regorafenib versus placebo was 4.5 versus 4.0 months (HR, 0.70; P = .011).

After preplanned adjustment for multiplicity, there were no statistically significant differences across regions (Asia vs. non-Asia) or other prespecified subgroups.

In the pooled analysis, which included study populations from both the INTEGRATE and INTEGRATE IIa populations, the median overall survival was 5.0 versus 4.1 (HR, 0.70; P = .001).  

Regorafenib also improved progression-free survival (median PFS, 1.8 vs. 1.6 months; HR, 0.52; P < .0001) and it delayed deterioration in global quality of life as compared with placebo (P = .0043).

Toxicity was similar to that previously reported in other studies, and adverse events were mostly grade 1 and 2.
 

A building block?

In a comment, Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Conn., said that she would consider the results with regorafenib in this setting as statistically significant, but with questionable clinical significance.

“The median overall survival difference 0.5 months or about 2 weeks is very modest, especially when taking into consideration the side effect profile,” she said. “I think that regorafenib as a building block for the additional phase 3 study is more interesting.”

“There is data that suggests synergy between VEGF inhibitors and immune checkpoint inhibitors, so I am eager to see the results of INEGRATE IIb [exploring regorafenib use with nivolumab],” Dr. Kunz added.

The study is sponsored by the Australasian Gastro-Intestinal Trials Group. Dr. Pavlakis reported relationships with Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Kunz reported relationships with Ipsen, Novartis (Advanced Accelerator Applications), Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and Isotope Technologies Munich.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Patients with refractory advanced gastroesophageal cancer (AGOC) have a poor prognosis, with limited options following failure of second-line therapy. New data showing improved survival suggest that regorafenib (Stivarga) may offer a new treatment option in these patients.

“Regorafenib significantly improves survival compared with placebo in patients with refractory AGOC, delaying deterioration in global quality of life,” said lead author Nick Pavlakis, PhD, MBBS, Royal North Shore Hospital, St. Leonards, Australia. “There were also no new toxicity signals.”

He emphasized that benefit was consistent in all preplanned subgroups. “This offers a new treatment option in this setting,” Dr. Pavlakis said.

He presented the findings at the ASCO Gastrointestinal Cancers Symposium 2023.

Regorafenib is an oral multikinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-beta, FGFR), and oncogenesis (RAF, RET, and KIT). It is already approved for several indications including metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma. 

AGOC could be a new indication for the drug. Use in this patient population was explored in an earlier trial, Dr. Pavlakis commented.

“We previously demonstrated the regorafenib prolonged progression-free survival in the INTEGRATE phase 2 trial,” he said. “Based on those results, we undertook the phase 3 INTEGRATE II study. The goal was to examine if regorafenib improves overall survival after failure of at least two lines of treatment.”

However, Dr. Pavlakis noted that during the conduct of this study, there was a change of practice in gastric cancer. “There was an evolution of new evidence in support of additional chemotherapy and immune checkpoint inhibitors such as nivolumab, and very interesting data on the combination of nivolumab and regorafenib from a study being conducted in Japan. So we amended the protocol and evolved the INTEGRATE II to INTEGRATE IIa, to continue evaluating regorafenib versus placebo, and then to evolve to the INTEGRATE IIb study to evaluate regorafenib plus nivolumab versus chemotherapy,” he explained.

The results he presented at the meeting came from the phase 3 INTEGRATE II part of this trial. The other part of the trial, INTEGRATE IIb, is still accruing.

A total of 251 patients were enrolled from five countries and stratified by tumor location, geographic location (Asia vs. “rest of the world”), and prior treatment with VEGF inhibitors.

The cohort was randomly assigned to receive 160 mg regorafenib and best supportive care or placebo plus BSC.

After 238 events, the overall survival hazard ratio was 0.68. “The survival benefit of regorafenib was best observed in the 12-month survival of 19% versus 6%,” said Pavlakis.

The median overall survival for regorafenib versus placebo was 4.5 versus 4.0 months (HR, 0.70; P = .011).

After preplanned adjustment for multiplicity, there were no statistically significant differences across regions (Asia vs. non-Asia) or other prespecified subgroups.

In the pooled analysis, which included study populations from both the INTEGRATE and INTEGRATE IIa populations, the median overall survival was 5.0 versus 4.1 (HR, 0.70; P = .001).  

Regorafenib also improved progression-free survival (median PFS, 1.8 vs. 1.6 months; HR, 0.52; P < .0001) and it delayed deterioration in global quality of life as compared with placebo (P = .0043).

Toxicity was similar to that previously reported in other studies, and adverse events were mostly grade 1 and 2.
 

A building block?

In a comment, Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Conn., said that she would consider the results with regorafenib in this setting as statistically significant, but with questionable clinical significance.

“The median overall survival difference 0.5 months or about 2 weeks is very modest, especially when taking into consideration the side effect profile,” she said. “I think that regorafenib as a building block for the additional phase 3 study is more interesting.”

“There is data that suggests synergy between VEGF inhibitors and immune checkpoint inhibitors, so I am eager to see the results of INEGRATE IIb [exploring regorafenib use with nivolumab],” Dr. Kunz added.

The study is sponsored by the Australasian Gastro-Intestinal Trials Group. Dr. Pavlakis reported relationships with Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Kunz reported relationships with Ipsen, Novartis (Advanced Accelerator Applications), Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and Isotope Technologies Munich.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – An experimental monoclonal antibody combined with chemotherapy could offer a new standard of care for patients with claudin-18.2+ (CLDN18.2+) / HER2− advanced gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, say researchers in reporting a phase 3 trial.

Used in the frontline setting, zolbetuximab (under development by Ganymed Pharmaceuticals AG) combined with chemotherapy led to significantly longer progression-free survival and overall survival, compared with what was seen with chemotherapy alone.

The chemotherapy used was the mFOLFOX6 regimen, comprising folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (OX).

“Zolbetuximab plus mFOLFOX6 is a new potential standard treatment for these patients,” said lead study author Kohei Shitara, MD, department of gastrointestinal oncology, National Cancer Center Hospital East Kashiwa City, Chiba, Japan.

This is one of the longest median overall survival outcomes for patients with locally advanced mG/GEJ adenocarcinoma in phase 3 trials, Dr. Shitera emphasized. “Survival benefits were observed across most subgroups,” he said. “Zolbetuximab plus mFOLFOX6 demonstrated a tolerable and manageable safety profile, and it was consistent with prior studies of the combination.”

The findings were presented at the 2023 Gastrointestinal Cancers Symposium.

Zolbetuximab is a monoclonal antibody that targets the cell surface molecule CLDN18.2, which is expressed in normal gastric mucosa cells and is retained in mG/GEJ tumor cells. It represents a unique target in that it is restricted to differentiated stomach cells only, and LDN18.2 is absent from all other healthy tissues.

However, it is upregulated in various cancers, including about 80% of gastrointestinal adenocarcinomas, 60% of pancreatic tumors, and biliary, ovarian, and lung cancers.

In a discussion of the paper, David H. Wang, MD, PhD, an associate professor in the department of internal medicine at University of Texas Southwestern Medical Center, Dallas, pointed out that “zolbetuximab is the first molecularly targeted therapy, exclusive of immune checkpoint inhibitors, to demonstrate a statistically significant survival benefit in first-line treatment of advanced gastric cancer since trastuzumab.”

But he asked why the control arm did so well.

One reason may be that claudin 18 positivity may be associated with a better prognosis for patients with diffuse gastric cancer, he explained. “It may also be due to more limited or earlier disease – the majority had limited metastases, and one-third had a prior gastrectomy.”

Overall, Dr. Wang believes that these results validate claudin 18 as a new predictive biomarker for advanced gastric cancer, although he noted that widespread implementation for this indication may be limited, as the assay to determine claudin 18 levels is not widely available. “Standardization is also needed for interpretation,” he added.
 

Study details

First-line therapy for HER2− mG/GEJ adenocarcinoma generally consists of chemotherapy and immunotherapy, but among patients with advanced disease, the prognosis continues to be poor, and therapeutic options are limited.

Zolbetuximab improved survival in the phase 2 FAST trial, which was conducted in a similar patient cohort. Median overall survival was significantly longer for patients who received zolbetuximab in comparison with those who did not (13.2 vs. 8.4 months). For patients with the highest levels of CLDN18.2, median overall survival was even longer (16.7 vs. 9.0 months).

“There is a need for better therapies, as chemotherapy is still the primary treatment,” said Dr. Shitera. “Some patients may benefit from targeted therapies, but clearly, better therapies are needed.”
 

Significantly improved survival

In the current phase 3 trial, dubbed SPOTLIGHT, Dr. Shitera and colleagues randomly assigned 565 patients to receive either zolbetuximab IV 800 mg/m² (cycle 1, day 1) followed by 600 mg/m² (cycle 1, day 22, and every 3 weeks in later cycles) plus mFOLFOX6 IV for four 42-day cycles or placebo plus mFOLFOX6.

All patients were treatment naive with CLDN18.2/HER2− locally advanced unresectable or metastatic mG/GEJ adenocarcinoma. Treatment continued until disease progression or discontinuation criteria were met.

The primary endpoint of progression-free survival was statistically significantly improved among patients who received combination therapy with zolbetuximab, compared with patients who received placebo (median 10.61 vs. 8.67 months; hazard ratio, 0.751; P = .0066).

“This was highly significant, and the study met its primary endpoint,” said Dr. Shitera. “The subgroup analysis shows that there was also consistent benefit in the prespecified subgroups.”

In similar fashion, overall survival was also significantly improved (median, 18.23 vs. 15.54 months; HR, 0.750; P = .0053).

However, the overall response rate was similar between groups (60.7% vs. 62.1%).

Toxicity was higher in the zolbetuximab group. The most common treatment-related adverse events were nausea (82.4% vs. 60.8% in zolbetuximab vs. placebo arms), vomiting (67.4% vs. 35.6%), and decreased appetite (47.0% vs. 33.5%), although the incidence of serious events was similar between the groups (44.8% vs. 43.5%).

Most events occurred at first or second cycle and could be resolved, Dr. Shitera noted, and treatment-related events were consistent with those of previous studies.

The study was funded by Astellas Pharma. Dr. Shitara has relationships with numerous pharmaceutical companies, as listed in the abstract.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – An experimental monoclonal antibody combined with chemotherapy could offer a new standard of care for patients with claudin-18.2+ (CLDN18.2+) / HER2− advanced gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, say researchers in reporting a phase 3 trial.

Used in the frontline setting, zolbetuximab (under development by Ganymed Pharmaceuticals AG) combined with chemotherapy led to significantly longer progression-free survival and overall survival, compared with what was seen with chemotherapy alone.

The chemotherapy used was the mFOLFOX6 regimen, comprising folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (OX).

“Zolbetuximab plus mFOLFOX6 is a new potential standard treatment for these patients,” said lead study author Kohei Shitara, MD, department of gastrointestinal oncology, National Cancer Center Hospital East Kashiwa City, Chiba, Japan.

This is one of the longest median overall survival outcomes for patients with locally advanced mG/GEJ adenocarcinoma in phase 3 trials, Dr. Shitera emphasized. “Survival benefits were observed across most subgroups,” he said. “Zolbetuximab plus mFOLFOX6 demonstrated a tolerable and manageable safety profile, and it was consistent with prior studies of the combination.”

The findings were presented at the 2023 Gastrointestinal Cancers Symposium.

Zolbetuximab is a monoclonal antibody that targets the cell surface molecule CLDN18.2, which is expressed in normal gastric mucosa cells and is retained in mG/GEJ tumor cells. It represents a unique target in that it is restricted to differentiated stomach cells only, and LDN18.2 is absent from all other healthy tissues.

However, it is upregulated in various cancers, including about 80% of gastrointestinal adenocarcinomas, 60% of pancreatic tumors, and biliary, ovarian, and lung cancers.

In a discussion of the paper, David H. Wang, MD, PhD, an associate professor in the department of internal medicine at University of Texas Southwestern Medical Center, Dallas, pointed out that “zolbetuximab is the first molecularly targeted therapy, exclusive of immune checkpoint inhibitors, to demonstrate a statistically significant survival benefit in first-line treatment of advanced gastric cancer since trastuzumab.”

But he asked why the control arm did so well.

One reason may be that claudin 18 positivity may be associated with a better prognosis for patients with diffuse gastric cancer, he explained. “It may also be due to more limited or earlier disease – the majority had limited metastases, and one-third had a prior gastrectomy.”

Overall, Dr. Wang believes that these results validate claudin 18 as a new predictive biomarker for advanced gastric cancer, although he noted that widespread implementation for this indication may be limited, as the assay to determine claudin 18 levels is not widely available. “Standardization is also needed for interpretation,” he added.
 

Study details

First-line therapy for HER2− mG/GEJ adenocarcinoma generally consists of chemotherapy and immunotherapy, but among patients with advanced disease, the prognosis continues to be poor, and therapeutic options are limited.

Zolbetuximab improved survival in the phase 2 FAST trial, which was conducted in a similar patient cohort. Median overall survival was significantly longer for patients who received zolbetuximab in comparison with those who did not (13.2 vs. 8.4 months). For patients with the highest levels of CLDN18.2, median overall survival was even longer (16.7 vs. 9.0 months).

“There is a need for better therapies, as chemotherapy is still the primary treatment,” said Dr. Shitera. “Some patients may benefit from targeted therapies, but clearly, better therapies are needed.”
 

Significantly improved survival

In the current phase 3 trial, dubbed SPOTLIGHT, Dr. Shitera and colleagues randomly assigned 565 patients to receive either zolbetuximab IV 800 mg/m² (cycle 1, day 1) followed by 600 mg/m² (cycle 1, day 22, and every 3 weeks in later cycles) plus mFOLFOX6 IV for four 42-day cycles or placebo plus mFOLFOX6.

All patients were treatment naive with CLDN18.2/HER2− locally advanced unresectable or metastatic mG/GEJ adenocarcinoma. Treatment continued until disease progression or discontinuation criteria were met.

The primary endpoint of progression-free survival was statistically significantly improved among patients who received combination therapy with zolbetuximab, compared with patients who received placebo (median 10.61 vs. 8.67 months; hazard ratio, 0.751; P = .0066).

“This was highly significant, and the study met its primary endpoint,” said Dr. Shitera. “The subgroup analysis shows that there was also consistent benefit in the prespecified subgroups.”

In similar fashion, overall survival was also significantly improved (median, 18.23 vs. 15.54 months; HR, 0.750; P = .0053).

However, the overall response rate was similar between groups (60.7% vs. 62.1%).

Toxicity was higher in the zolbetuximab group. The most common treatment-related adverse events were nausea (82.4% vs. 60.8% in zolbetuximab vs. placebo arms), vomiting (67.4% vs. 35.6%), and decreased appetite (47.0% vs. 33.5%), although the incidence of serious events was similar between the groups (44.8% vs. 43.5%).

Most events occurred at first or second cycle and could be resolved, Dr. Shitera noted, and treatment-related events were consistent with those of previous studies.

The study was funded by Astellas Pharma. Dr. Shitara has relationships with numerous pharmaceutical companies, as listed in the abstract.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – An experimental monoclonal antibody combined with chemotherapy could offer a new standard of care for patients with claudin-18.2+ (CLDN18.2+) / HER2− advanced gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, say researchers in reporting a phase 3 trial.

Used in the frontline setting, zolbetuximab (under development by Ganymed Pharmaceuticals AG) combined with chemotherapy led to significantly longer progression-free survival and overall survival, compared with what was seen with chemotherapy alone.

The chemotherapy used was the mFOLFOX6 regimen, comprising folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (OX).

“Zolbetuximab plus mFOLFOX6 is a new potential standard treatment for these patients,” said lead study author Kohei Shitara, MD, department of gastrointestinal oncology, National Cancer Center Hospital East Kashiwa City, Chiba, Japan.

This is one of the longest median overall survival outcomes for patients with locally advanced mG/GEJ adenocarcinoma in phase 3 trials, Dr. Shitera emphasized. “Survival benefits were observed across most subgroups,” he said. “Zolbetuximab plus mFOLFOX6 demonstrated a tolerable and manageable safety profile, and it was consistent with prior studies of the combination.”

The findings were presented at the 2023 Gastrointestinal Cancers Symposium.

Zolbetuximab is a monoclonal antibody that targets the cell surface molecule CLDN18.2, which is expressed in normal gastric mucosa cells and is retained in mG/GEJ tumor cells. It represents a unique target in that it is restricted to differentiated stomach cells only, and LDN18.2 is absent from all other healthy tissues.

However, it is upregulated in various cancers, including about 80% of gastrointestinal adenocarcinomas, 60% of pancreatic tumors, and biliary, ovarian, and lung cancers.

In a discussion of the paper, David H. Wang, MD, PhD, an associate professor in the department of internal medicine at University of Texas Southwestern Medical Center, Dallas, pointed out that “zolbetuximab is the first molecularly targeted therapy, exclusive of immune checkpoint inhibitors, to demonstrate a statistically significant survival benefit in first-line treatment of advanced gastric cancer since trastuzumab.”

But he asked why the control arm did so well.

One reason may be that claudin 18 positivity may be associated with a better prognosis for patients with diffuse gastric cancer, he explained. “It may also be due to more limited or earlier disease – the majority had limited metastases, and one-third had a prior gastrectomy.”

Overall, Dr. Wang believes that these results validate claudin 18 as a new predictive biomarker for advanced gastric cancer, although he noted that widespread implementation for this indication may be limited, as the assay to determine claudin 18 levels is not widely available. “Standardization is also needed for interpretation,” he added.
 

Study details

First-line therapy for HER2− mG/GEJ adenocarcinoma generally consists of chemotherapy and immunotherapy, but among patients with advanced disease, the prognosis continues to be poor, and therapeutic options are limited.

Zolbetuximab improved survival in the phase 2 FAST trial, which was conducted in a similar patient cohort. Median overall survival was significantly longer for patients who received zolbetuximab in comparison with those who did not (13.2 vs. 8.4 months). For patients with the highest levels of CLDN18.2, median overall survival was even longer (16.7 vs. 9.0 months).

“There is a need for better therapies, as chemotherapy is still the primary treatment,” said Dr. Shitera. “Some patients may benefit from targeted therapies, but clearly, better therapies are needed.”
 

Significantly improved survival

In the current phase 3 trial, dubbed SPOTLIGHT, Dr. Shitera and colleagues randomly assigned 565 patients to receive either zolbetuximab IV 800 mg/m² (cycle 1, day 1) followed by 600 mg/m² (cycle 1, day 22, and every 3 weeks in later cycles) plus mFOLFOX6 IV for four 42-day cycles or placebo plus mFOLFOX6.

All patients were treatment naive with CLDN18.2/HER2− locally advanced unresectable or metastatic mG/GEJ adenocarcinoma. Treatment continued until disease progression or discontinuation criteria were met.

The primary endpoint of progression-free survival was statistically significantly improved among patients who received combination therapy with zolbetuximab, compared with patients who received placebo (median 10.61 vs. 8.67 months; hazard ratio, 0.751; P = .0066).

“This was highly significant, and the study met its primary endpoint,” said Dr. Shitera. “The subgroup analysis shows that there was also consistent benefit in the prespecified subgroups.”

In similar fashion, overall survival was also significantly improved (median, 18.23 vs. 15.54 months; HR, 0.750; P = .0053).

However, the overall response rate was similar between groups (60.7% vs. 62.1%).

Toxicity was higher in the zolbetuximab group. The most common treatment-related adverse events were nausea (82.4% vs. 60.8% in zolbetuximab vs. placebo arms), vomiting (67.4% vs. 35.6%), and decreased appetite (47.0% vs. 33.5%), although the incidence of serious events was similar between the groups (44.8% vs. 43.5%).

Most events occurred at first or second cycle and could be resolved, Dr. Shitera noted, and treatment-related events were consistent with those of previous studies.

The study was funded by Astellas Pharma. Dr. Shitara has relationships with numerous pharmaceutical companies, as listed in the abstract.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

A version of this article first appeared on Medscape.com.

Current guidelines recommend against screening for prostate cancer in men who are 70 years old and older, as it is considered to be “low value” with little or no benefit for the individual. Yet a new study shows that testing for prostate-specific antigen (PSA) and also digital rectal examinations (DRE) are both carried out frequently in older men, even when there is no indication for such testing.

“As a man ages, the risk for a false-positive result increases,” said lead author Chris Gillette, PhD, associate professor of physician assistant studies at Wake Forest University, Winston-Salem, N.C., in a statement

The study authors looked at primary care visits for men who were age 70 or older, and found that, per 100 visits, there were 6.7 PSA tests and 1.6 DRE performed.

Dr. Gillette and colleagues emphasized the importance of their findings. Whereas prior studies have relied on commercially insured men or patient-reported rates of PSA testing, they used a nationally representative clinical dataset that is much more inclusive, as it includes men who are also uninsured or insured through traditional Medicare.

The study was published online in the Journal of the American Board of Family Medicine.

Screening for prostate cancer has been much debated, and the guidelines have changed in recent years. In the period 2012-2018, the U.S. Preventive Services Task Force recommended against PSA-based screening in all men, but then the guidelines changed, and the USPSTF subsequently endorsed individualized screening in those aged 55-69 years after a shared decision-making discussion. That same 2018 update also recommends against PSA screening in men over the age of 70.

In addition, the American Urological Association has recommended against PSA-based prostate cancer screening for men over the age of 70 since 2013.

Previous studies have shown that clinicians are not adhering to the guidelines. An analysis conducted in March 2022 found that about one in four accredited U.S. cancer centers fails to follow national guidelines for PSA testing to screen for prostate cancer. Contrary to national guidelines, which advocate shared decision-making, 22% of centers recommend all men universally initiate PSA screening at either age 50 or 55 and another 4% of centers recommend this before age 50, earlier than the guidelines advise.

In the current study, Dr. Gillette and colleagues conducted a secondary analysis of the National Ambulatory Medical Care Survey datasets from 2013 to 2016 and 2018. The dataset is a nationally representative sample of visits to nonfederal, office-based physician clinics. This analysis was restricted to male patients aged 70 years and older who visited a primary care clinic.

The team found that health care professionals who order a lot of tests are more likely to order low-value screening such as PSA and DRE.

The data also showed that when there were a higher number of services ordered/provided, the patients were significantly more likely to receive a low-value PSA (odds ratio, 1.49) and a low-value DRE (OR, 1.37). In contrast, patients who had more previous visits to the clinician were less likely to receive a low-value DRE (OR, 0.92).

Overall, there a decline in low-value PSA screening after 2014, but this trend was not seen for DRE during primary care visits.

Speculating as to why these low-value tests are being carried out, Dr. Gillette suggested that health care professionals might be responding to patient requests when ordering these screening tests, or they may be using what’s known as a “shotgun” approach to medical testing where all possible tests are ordered during a medical visit.

“However, as health care systems move toward a more value-based care system – where the benefit of services provided outweighs any risks – clinicians need to engage patients in these discussions on the complexity of this testing,” he commented. “Ultimately, when and if to screen is a decision best left between a provider and the patient.”

There was no outside funding and the authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Current guidelines recommend against screening for prostate cancer in men who are 70 years old and older, as it is considered to be “low value” with little or no benefit for the individual. Yet a new study shows that testing for prostate-specific antigen (PSA) and also digital rectal examinations (DRE) are both carried out frequently in older men, even when there is no indication for such testing.

“As a man ages, the risk for a false-positive result increases,” said lead author Chris Gillette, PhD, associate professor of physician assistant studies at Wake Forest University, Winston-Salem, N.C., in a statement

The study authors looked at primary care visits for men who were age 70 or older, and found that, per 100 visits, there were 6.7 PSA tests and 1.6 DRE performed.

Dr. Gillette and colleagues emphasized the importance of their findings. Whereas prior studies have relied on commercially insured men or patient-reported rates of PSA testing, they used a nationally representative clinical dataset that is much more inclusive, as it includes men who are also uninsured or insured through traditional Medicare.

The study was published online in the Journal of the American Board of Family Medicine.

Screening for prostate cancer has been much debated, and the guidelines have changed in recent years. In the period 2012-2018, the U.S. Preventive Services Task Force recommended against PSA-based screening in all men, but then the guidelines changed, and the USPSTF subsequently endorsed individualized screening in those aged 55-69 years after a shared decision-making discussion. That same 2018 update also recommends against PSA screening in men over the age of 70.

In addition, the American Urological Association has recommended against PSA-based prostate cancer screening for men over the age of 70 since 2013.

Previous studies have shown that clinicians are not adhering to the guidelines. An analysis conducted in March 2022 found that about one in four accredited U.S. cancer centers fails to follow national guidelines for PSA testing to screen for prostate cancer. Contrary to national guidelines, which advocate shared decision-making, 22% of centers recommend all men universally initiate PSA screening at either age 50 or 55 and another 4% of centers recommend this before age 50, earlier than the guidelines advise.

In the current study, Dr. Gillette and colleagues conducted a secondary analysis of the National Ambulatory Medical Care Survey datasets from 2013 to 2016 and 2018. The dataset is a nationally representative sample of visits to nonfederal, office-based physician clinics. This analysis was restricted to male patients aged 70 years and older who visited a primary care clinic.

The team found that health care professionals who order a lot of tests are more likely to order low-value screening such as PSA and DRE.

The data also showed that when there were a higher number of services ordered/provided, the patients were significantly more likely to receive a low-value PSA (odds ratio, 1.49) and a low-value DRE (OR, 1.37). In contrast, patients who had more previous visits to the clinician were less likely to receive a low-value DRE (OR, 0.92).

Overall, there a decline in low-value PSA screening after 2014, but this trend was not seen for DRE during primary care visits.

Speculating as to why these low-value tests are being carried out, Dr. Gillette suggested that health care professionals might be responding to patient requests when ordering these screening tests, or they may be using what’s known as a “shotgun” approach to medical testing where all possible tests are ordered during a medical visit.

“However, as health care systems move toward a more value-based care system – where the benefit of services provided outweighs any risks – clinicians need to engage patients in these discussions on the complexity of this testing,” he commented. “Ultimately, when and if to screen is a decision best left between a provider and the patient.”

There was no outside funding and the authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Current guidelines recommend against screening for prostate cancer in men who are 70 years old and older, as it is considered to be “low value” with little or no benefit for the individual. Yet a new study shows that testing for prostate-specific antigen (PSA) and also digital rectal examinations (DRE) are both carried out frequently in older men, even when there is no indication for such testing.

“As a man ages, the risk for a false-positive result increases,” said lead author Chris Gillette, PhD, associate professor of physician assistant studies at Wake Forest University, Winston-Salem, N.C., in a statement

The study authors looked at primary care visits for men who were age 70 or older, and found that, per 100 visits, there were 6.7 PSA tests and 1.6 DRE performed.

Dr. Gillette and colleagues emphasized the importance of their findings. Whereas prior studies have relied on commercially insured men or patient-reported rates of PSA testing, they used a nationally representative clinical dataset that is much more inclusive, as it includes men who are also uninsured or insured through traditional Medicare.

The study was published online in the Journal of the American Board of Family Medicine.

Screening for prostate cancer has been much debated, and the guidelines have changed in recent years. In the period 2012-2018, the U.S. Preventive Services Task Force recommended against PSA-based screening in all men, but then the guidelines changed, and the USPSTF subsequently endorsed individualized screening in those aged 55-69 years after a shared decision-making discussion. That same 2018 update also recommends against PSA screening in men over the age of 70.

In addition, the American Urological Association has recommended against PSA-based prostate cancer screening for men over the age of 70 since 2013.

Previous studies have shown that clinicians are not adhering to the guidelines. An analysis conducted in March 2022 found that about one in four accredited U.S. cancer centers fails to follow national guidelines for PSA testing to screen for prostate cancer. Contrary to national guidelines, which advocate shared decision-making, 22% of centers recommend all men universally initiate PSA screening at either age 50 or 55 and another 4% of centers recommend this before age 50, earlier than the guidelines advise.

In the current study, Dr. Gillette and colleagues conducted a secondary analysis of the National Ambulatory Medical Care Survey datasets from 2013 to 2016 and 2018. The dataset is a nationally representative sample of visits to nonfederal, office-based physician clinics. This analysis was restricted to male patients aged 70 years and older who visited a primary care clinic.

The team found that health care professionals who order a lot of tests are more likely to order low-value screening such as PSA and DRE.

The data also showed that when there were a higher number of services ordered/provided, the patients were significantly more likely to receive a low-value PSA (odds ratio, 1.49) and a low-value DRE (OR, 1.37). In contrast, patients who had more previous visits to the clinician were less likely to receive a low-value DRE (OR, 0.92).

Overall, there a decline in low-value PSA screening after 2014, but this trend was not seen for DRE during primary care visits.

Speculating as to why these low-value tests are being carried out, Dr. Gillette suggested that health care professionals might be responding to patient requests when ordering these screening tests, or they may be using what’s known as a “shotgun” approach to medical testing where all possible tests are ordered during a medical visit.

“However, as health care systems move toward a more value-based care system – where the benefit of services provided outweighs any risks – clinicians need to engage patients in these discussions on the complexity of this testing,” he commented. “Ultimately, when and if to screen is a decision best left between a provider and the patient.”

There was no outside funding and the authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Topical minoxidil is widely used to treat hair loss, but new findings suggest that a combination of oral and topical minoxidil could be effective for women with breast cancer who have experienced alopecia from anticancer treatment.

In a retrospective cohort study of women with breast cancer and anticancer therapy–induced alopecia, researchers found that combining low-dose oral minoxidil (LDOM) and topical minoxidil achieved better results than topical minoxidil alone and that the treatment was well tolerated. A total of 5 of the 37 patients (13.5%) in the combination therapy group achieved a complete response, defined as an improvement of alopecia severity from grade 2 to grade 1, compared with none of the 19 patients in the topical therapy–only group.

In contrast, none of the patients in the combination group experienced worsening of alopecia, compared with two (10.5%) in the topical monotherapy group.

The study was published online in the Journal of the American Academy of Dermatology. Topical minoxidil is approved by the Food and Drug Administration to treat androgenetic alopecia. Oral minoxidil is not approved for treating hair loss but has been receiving increased attention as an adjunctive therapy for hair loss, particularly for women. Oral minoxidil is approved for treating hypertension but at much higher doses.

An increasing number of studies have been conducted on the use of oral minoxidil for the treatment of female pattern hair loss, dating back to a pilot study in 2017, with promising results. The findings suggest that LDOM might be more effective than topical therapy, well tolerated, and more convenient for individuals to take.

Hypothesis generating

In a comment, Kai Johnson, MD, a medical oncologist who specializes in treating patients with breast cancer at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, noted that the study, like most small-scale retrospective studies, is hypothesis generating. However, “I’d be hesitant to broadly recommend this practice of dual therapy – oral and topical minoxidil together – until we see a placebo-controlled prospective study performed demonstrating clinically meaningful benefits for patients.”

Another factor is the study endpoints. “While there was a statistically significant benefit documented with dual therapy in this study, it’s important to have study endpoints that are more patient oriented,” Dr. Johnson said. The most important endpoint for patients would be improvements “in the actual alopecia grade, which did occur in 5 of the 37 of dual-therapy patients, versus 0 topical minoxidil patients.”

George Cotsarelis, MD, chair of the department of dermatology and professor of dermatology at the University of Pennsylvania, Philadelphia, also weighed in. He questioned whether adding the topical therapy to oral minoxidil actually improved the results. “What was missing was a study arm that used the oral alone,” he said in an interview. “So we don’t know how effective the oral therapy would be by itself and if combining it with the topical is really adding anything.”

Oral minoxidil as a treatment for hair loss is gaining traction, and it’s clear that it is effective. However, the risk of side effects is higher, he said. “The risk isn’t that high with the low dose, but it can grow hair on places other than the scalp, and that can be disconcerting.” In this study, two women who took the oral drug reported edema, and one reported headache and dizziness. Hypertrichosis was reported by five patients who received the combination.
 

Study details

In the study, Jeewoo Kang, MD, and colleagues from the Seoul National University evaluated the efficacy of LDOM in 100 patients with breast cancer who had been diagnosed with persistent chemotherapy-induced alopecia (pCIA) and endocrine therapy–induced alopecia (EIA) at a dermatology clinic.

They conducted an analysis of medical records, standardized clinical photographs, and trichoscopic images to evaluate the alopecia pattern, severity, treatment response, and posttreatment changes in vertex hair density and thickness.

Compared with those with EIA alone, patients with pCIA were significantly more likely to have diffuse alopecia (P < .001), and they were more likely to have more severe alopecia, although this difference was not significant (P = .058). Outcomes were evaluated for 56 patients who were treated with minoxidil (19 with topical minoxidil alone and 37 with both LDOM and topical minoxidil) and for whom clinical and trichoscopic photos were available at baseline and at the last follow-up (all patients were scheduled for follow-up at 3-month intervals).

The results showed that those treated with 1.25-5.0 mg/d of oral minoxidil and 5% topical minoxidil solution once a day had better responses (P = .002) and a higher percentage increase in hair density from baseline (P = .003), compared with those who received topical minoxidil monotherapy.

However, changes in hair thickness after treatment were not significantly different between the two groups (P = .540).

In addition to the five (13.5%) cases of hypertrichosis, two cases of edema (5.4%), and one case of headache/dizziness (2.7%) among those who received the combination, there was also one report of palpitations (2.7%). Palpitations were reported in one patient (5%) who received topical monotherapy, the only adverse event reported in this group.

Dr. Johnson noted that, at his institution, a dermatologist is conducting a clinical trial with oncology patients post chemotherapy and endocrine therapy. “She is looking at a similar question, although she is comparing oral minoxidil to topical minoxidil directly rather than in combination.” There is also an active clinical trial at Northwestern University, Chicago, of LDOM alone for patients with chemotherapy-induced alopecia.

“So there is a lot of momentum surrounding this concept, and I feel we will continue to see it come up as a possible treatment option, but more data are needed at this time before it can become standard of care,” Dr. Johnson added.

No funding for the study was reported. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

A version of this article first appeared on Medscape.com.

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

A version of this article first appeared on Medscape.com.

Much attention has been given recently to the idea of detecting many different types of cancer from a single blood test, and a new test claiming to do that has just been reported.

The leader in this field is the Galleri test (from GRAIL) which is already in clinical use in some health care networks across the United States. That test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating tumor (or cell-free) DNA (cfDNA) in a blood sample.

The new test, under development by Swedish biotechnology company Elypta AB, has a different premise. It can detect 14 cancer types based on the analysis of glycosaminoglycans, which are a diverse group of polysaccharides that are altered by the presence of tumors. Using plasma and urine samples, the method had a 41.6%-62.3% sensitivity for detecting stage I cancer at 95% specificity.

In comparison, say the authors, other assays have reported 39%-73% sensitivity to stage I cancers, but these estimates are usually limited to 12 cancer types that are considered “high-signal,” and the assays perform poorly in cancers that emit little cfDNA, such as genitourinary and brain malignancies.

“The main advantage of glycosaminoglycans appears to be that they change in the blood and urine at the earliest stages of cancer,” said study author Francesco Gatto, PhD, founder and chief scientific officer at Elypta. “Consequently, this method showed an impressive detection rate in stage I compared to other emerging methods.”

The study was published online in Proceedings of the National Academy of Sciences.


 

Combine tests?

Dr. Gatto commented that he “could envision that one day we may be able to combine these methods.”

“The same blood specimen could be used to test both glycosaminoglycans and genomic biomarkers,” said Dr. Gatto. “This strategy could hopefully detect even more cancers than with either method alone, and the resulting performance may well be sufficient as a one-stop-shop screening program.”

So how does the new test from Elypta compare with the Galleri test?

“Galleri and similar methods mostly focused on information coming from molecules of DNA naturally floating in the blood,” explained Dr. Gatto. “It makes sense to conduct research there because cancers typically start with events in the DNA.”

He noted that the current study explored a new layer of information, molecules called glycosaminoglycans, that participate in the metabolism of cancer.

“This method detected many cancers that the previous methods missed, and a substantial proportion of these were at stage I,” said Dr. Gatto. “Cancer is a complex disease, so the most layers of information we can probe noninvasively, say with a blood test, the more likely we can catch more cancers at its earliest stage.”

Other platforms typically rely on sequencing and detecting cancer-derived fractions of cfDNA, but these methods have challenges that can interfere with their usage. For example, some cancer types do not shed sufficient cfDNA and it cannot be accurately measured.

“An advantage on focusing on glycosaminoglycans is that the method does not require next-generation sequencing or similarly complex assays because glycosaminoglycans are informative with less than 10 simultaneous measurements as opposed to Galleri that looks at over 1 million DNA methylation sites,” he said.

“This makes the assay behind the test much cheaper and robust – we estimated a 5-10 times lower cost difference,” Dr. Gatto said.
 

Prospective and comparative data needed

In a comment, Eric Klein, MD, emeritus chair of the Glickman Urological and Kidney Institute at the Cleveland Clinic explained that the “only accurate way to know how a test will perform in an intended-use population is to actually test it in that population. It’s not possible to extrapolate results directly from a case-control study.”

Cancers shed many different biologic markers into body fluids, but which of these signals will be best to serve as the basis of an MCED (multi-cancer detection test) that has clinical utility in a screening population has yet to be determined, he noted. “And it’s possible that no single test will be optimum for every clinical situation.”

“The results of this study appear promising, but it is not possible to claim superiority of one test over another based on individual case-control studies because of uncontrolled differences in the selected populations,” Dr. Klein continued. “The only scientifically accurate way to do this is to perform different tests on the same patient samples in a head-to-head comparison.”

There is only one study that he is aware of that has done this recently, in which multiple different assays looking at various signals in cell-free DNA were directly compared on the same samples (Cancer cell. 2022;40:1537-49.e12). “A targeted methylation assay that is the basis for Galleri was best for the lowest limit of detection and for predicting cancer site of origin,” said Dr. Klein.

Another expert agreed that a direct head-to-head study is needed to compare assays. “Based on this data, you cannot say that this method is better than the other one because that requires a comparative study,” said Fred Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology, Tisch Cancer Institute at Mount Sinai, New York.

Metabolomics is interesting, and the data are encouraging, he continued. “But this is a multicancer early detection test and metabolism changes may vary from cancer type to cancer type. I’m not sure that the metabolism of lung cancer is the same as that of a gynecologic cancer.”

Dr. Hirsch also pointed out that there could also be confounding factors. “They have excluded inflammatory disease, but there can be other variables such as smoking,” he said. “Overall it gives some interesting perspectives but I would like to see more prospective validation and studies in specific disease groups, and eventually comparative studies with other methodologies.”
 

Study details

The authors evaluated if plasma and urine free GAGomes (free glycosaminoglycan profiles) deviated from baseline physiological levels in 14 cancer types and could serve as metabolic cancer biomarkers. They also then validated using free GAGomes for MCED in an external population with 2,064 samples obtained from 1,260 patients with cancer and healthy individuals.

In an in vivo cancer progression model, they observed widespread cancer-specific changes in biofluidic free GAGomes and then developed three machine-learning models based on urine (n_urine = 220 cancer vs. 360 healthy) and plasma (n_plasma = 517 cancer vs. 425 healthy) free GAGomes that were able to detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 (with up to 62% sensitivity to stage I disease at 95% specificity).

To assess if altered GAGome features associated with cancer suggested more aggressive tumor biology, they correlated each score with overall survival. The median follow-up time was 17 months in the plasma cohort (n = 370 across 13 cancer types), 15 months in the urine cohort (n = 162 across 4 cancer types), and 15 months in the combined cohort (n = 152 across 4 cancer types).

They found that all three scores independently predicted overall survival in a multivariable analysis (hazard ratio, 1.29; P = .0009 for plasma; HR, 1.79; P = .0009 for urine; HR, 1.91; P = .0004 for combined) after adjusting for cancer type, age, sex, and stage IV or high-grade disease.

These findings showed an association of free GAGome alterations with aggressive cancer phenotypes and suggested that scores below the 95% specificity cutoff might have a better prognosis, the authors comment.

In addition, other analyses showed that free GAGomes predicted the putative cancer location with 89% accuracy. And finally, to confirm whether the free GAGome MCED scores could be used for screening, a validation analysis was conducted using a typical “screening population,” which requires at least 99% specificity. The combined free GAGomes were able to predict a poor prognosis of any cancer type within 18 months and with 43% sensitivity (21% in stage I; n = 121 and 49 cases).

Dr. Gatto believes that these results, as well as those from other studies looking at glycosaminoglycans as cancer biomarkers, will lead to the next steps of development. “But I speculate that this test could be most useful to assess in a cheap, practical, and noninvasive manner if a person at increased risk of cancer should be selected for cancer screening as part of established or emerging screening programs.”

The study was sponsored by Elypta. Dr. Gatto is listed as an inventor in patent applications related to the biomarkers described in this study and later assigned to Elypta, and is a shareholder and employed at Elypta. Dr. Hirsch reports no relevant financial relationships. Dr. Klein is a consultant for GRAIL and an investigator for CCGA and Pathfinder.

A version of this article first appeared on Medscape.com.

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

A version of this article first appeared on Medscape.com.

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

A version of this article first appeared on Medscape.com.

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%. Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Though more data are needed and the findings verified in other studies, the use of a different term such as “melanocytic neoplasm of low malignant potential” may be more appropriate and may help to begin to address the problem of overdiagnosis, they note.

“While the topic of very low-risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, of the department of medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using SEER data.”

She emphasized that currently, they do not propose any change to treatment of these lesions, just a change to the terminology. “A diagnosis of ‘MNLMP’ rather than ‘melanoma’ may potentially alleviate people’s concerns related to prognosis and begin to address the problem of overdiagnosis,” said Ms. Eguchi. The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors, the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current American Joint Committee on Cancer (AJCC) staging system.

There is evidence that the increasing incidence of melanoma is partly due to overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis, cases that could potentially be part of the phenomenon of overdiagnosis.

Subsets with low and high risk for death

In the study, Ms. Eguchi and colleagues analyzed information from the United States Surveillance, Epidemiology, and End Results (SEER) database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was less than or equal to 1.0 mm in thickness and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, then the ability of the models to identify very‐low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range, 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 of 7,652 (2.3%) patients died of melanoma within 7 years, and numbers were similar in the testing set (115 of 3,942; 2.9%).

Overall, the investigators identified three large subsets of patients who were in the AJCC seventh edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (Model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed as very low risk.

In Model 1B, the same initial classification was used, but it was further refined and limited to patients who were either age 43 years or younger or 44-69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis, this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (Model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher, compared with most patients with T1b tumors.

This study was supported by the National Cancer Institute. Ms. Eguchi had no disclosures to report.

A version of this article first appeared on Medscape.com.