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25% of patients with cancer lack immunity against measles
Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.
“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.
Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.
So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.
They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.
The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.
“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.
And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.
“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.
In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said
“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.
The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
Three subgroups more likely to have deficits
The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits: those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.
In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.
As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.
A study author explained why the study included mumps, a less threatening infection.
“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.
Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.
The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.
“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.
Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.
So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.
They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.
The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.
“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.
And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.
“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.
In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said
“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.
The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
Three subgroups more likely to have deficits
The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits: those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.
In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.
As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.
A study author explained why the study included mumps, a less threatening infection.
“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.
Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.
The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.
“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.
Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.
So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.
They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.
The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.
“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.
And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.
“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.
In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said
“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.
The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
Three subgroups more likely to have deficits
The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits: those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.
In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.
As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.
A study author explained why the study included mumps, a less threatening infection.
“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.
Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.
The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.
A version of this article first appeared on Medscape.com.
‘Routine’ use of focal therapy for prostate cancer in next 5 years
They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.
Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.
The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.
“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.
But payees are already making changes, even without such data, they add.
For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services
This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.
“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”
The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.
Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
While waiting for CHRONOS, select wisely
The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”
However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.
Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.
They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”
Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
What is that evidence?
In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).
However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.
Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.
Meanwhile, careful patient selection is very important, they say.
The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.
A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.
UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.
To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”
Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.
Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.
A version of this article first appeared on Medscape.com.
They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.
Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.
The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.
“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.
But payees are already making changes, even without such data, they add.
For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services
This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.
“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”
The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.
Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
While waiting for CHRONOS, select wisely
The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”
However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.
Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.
They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”
Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
What is that evidence?
In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).
However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.
Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.
Meanwhile, careful patient selection is very important, they say.
The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.
A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.
UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.
To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”
Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.
Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.
A version of this article first appeared on Medscape.com.
They maintain that focal therapy (FT) offers a “middle ground” between two extremes: Treating the whole gland with radical prostatectomy or radiotherapy and not treating immediately via active surveillance or watchful waiting.
Focal therapy typically treats the primary lesion within the prostate, while leaving the rest of the gland intact. Most often performed with cryoablation or high-intensity focused ultrasound (HIFU), it can also be carried out with a variety of technologies, including transurethral ultrasound ablation and focal laser ablation.
The shift to focal therapy will coincide with maturing, long-term data from studies with various technologies, predict the authors, led by Amir Lebastchi, MD, a urologist at the University of Southern California.
“Standard adoption of focal therapy is ultimately dependent on the availability of robust level I evidence, which in turn will drive medical societies and payees,” the authors also write.
But payees are already making changes, even without such data, they add.
For example, in January the American Medical Association announced a new code for high-intensity focal ultrasound (HIFU): This approach now has a Current Procedural Terminology (CPT) code from the U.S. Centers for Medicare & Medicaid Services
This news organization reached out to Matthew Cooperberg, MD, MPH, a urologist at the University of California, San Francisco (UCSF), for comments about the essay’s optimism; he has questioned focal therapy in the past because of a lack of strong supporting evidence.
“While ‘routine’ is a bit of a vague term, now that HIFU has a CPT code, I do expect its use will in fact increase in the next 5 years,” Dr. Cooperberg wrote in an email. “The question is whether its use will increase appropriately.”
The challenge with focal therapy – regardless of energy modality – remains patient selection and accurate ablation zone definition, he added.
Notably, UCSF has launched a new HIFU program – and Dr. Cooperberg has referred selected patients. “I’m both enthusiastic and cautious about the future, and we need to track our outcomes very closely across various practice settings,” he said.
While waiting for CHRONOS, select wisely
The goal of focal therapy is to treat only the area with the most aggressive tumor, known as the index tumor, while leaving the remaining gland and its surrounding structures alone, according to Derek Lomas, MD, PharmD, a urologist at the Mayo Clinic in Rochester, Minn., in an explanatory article. “This approach is widely accepted in other types of cancer. For example, we commonly treat kidney cancers by removing or ablating only the tumor while leaving the rest of the kidney intact.”
However, some focal therapies also include approaches known as hemiablations, in which a full half of the prostate is destroyed, and approaches that leave very little of the gland behind.
Each of the modalities used for focal therapy has “unique indications, risks, and benefits and uses a different energy source for ablation,” Dr. Lebastchi and colleagues write in their essay.
They assert that focal therapy can provide oncological efficacy similar to radical prostatectomy or radiotherapy “while considerably reducing or even eliminating functional morbidities, such as incontinence and erectile dysfunction.”
Overall, they say focal therapy offers an opportunity for improved care because there is “an increasing body of emerging evidence demonstrating a favorable adverse effect profile with oncological control similar to whole-gland treatment options.”
What is that evidence?
In the essay, Dr. Lebastchi and colleagues point to a number of single-arm studies with encouraging efficacy and safety results. They also highlight a phase 3, randomized trial that they were involved in: This compared focal therapy (partial gland ablation with vascular-targeted photodynamic therapy) with active surveillance in early-stage disease and uniformly showed better post-treatment biopsy (disease/no disease) and conversion-to-prostatectomy results with the focal therapy out to 4 years (J Urol. 2018;200:786-793).
However, that study did not have an active treatment comparator. For that gold standard, there is now anticipation for results from the CHRONOS trial in the United Kingdom, especially part A of the trial, which compares radical therapy to focal therapy (HIFU or cryotherapy), with 5-year progression-free survival as the primary outcome. That trial is slated for completion in 2027.
Until then, the lack of prospective randomized clinical trials and long-term follow-up “hinders acceptance [of focal therapy] in the urology community,” the essay authors comment.
Meanwhile, careful patient selection is very important, they say.
The latest relevant guidelines state that appropriate candidates are men with a solitary, well-defined index lesion; patients with bilateral multifocal lesions; or very advanced tumors that are not appropriate for the focal approach.
A multidisciplinary international expert panel recently convened to establish guidance for clinicians offering focal therapies and then published a consensus statement to advise practitioners and researchers.
UCSF’s Dr. Cooperberg sees plenty of room for improvement among focal therapy practitioners and investigators. “From an outcomes standpoint, follow-up protocols and definitions of success remain inconsistent. I believe we’re making progress in all these areas, but we’re not there yet,” he says.
To date, some patients have been managed poorly, Dr. Cooperberg added. “We certainly see many patients who have been inadequately counseled as to HIFU’s advantages and disadvantages, with sometimes disastrous results.”
Some of those unfortunate results may have arisen from the U.S. Food and Drug Administration’s initial approval of HIFU in 2015, which was for use in ablating prostate tissue in general and not cancer specifically. This approval generated confusion, one expert commented at the time: “The FDA doesn’t specify whether it’s for benign or malignant disease; it’s a bit vague, like saying you can drive this car, but we’re not going to tell you how to drive it,” said Manoj Monga, MD, from the Cleveland Clinic.
Dr. Lebastchi has disclosed no relevant financial relationships; co-author Inderbir Gill, MD, is an unpaid consultant for Steba Biotech, and co-author Andre Luis Abreu, MD, is a consultant for Koelis and was a proctor in training for Steba Biotech. Dr. Cooperberg is a consultant for Alessa Therapeutics.
A version of this article first appeared on Medscape.com.
One in three cancer articles on social media has wrong info
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Of the 200 most popular articles (50 each for prostate, lung, breast, and colorectal cancer), about a third (32.5%, n = 65) contained misinformation.
Among these articles containing misinformation, 76.9% (50/65) contained harmful information.
“The Internet is a leading source of health misinformation,” the study authors wrote. This is “particularly true for social media, where false information spreads faster and more broadly than fact-checked information,” they said, citing other research.
“We need to address these issues head on,” said lead author Skyler Johnson, MD, of the University of Utah’s Huntsman Cancer Institute in Salt Lake City.
“As a medical community, we can’t ignore the problem of cancer misinformation on social media or ask our patients to ignore it. We must empathize with our patients and help them when they encounter this type of information,” he said in a statement. “My goal is to help answer their questions, and provide cancer patients with accurate information that will give them the best chance for the best outcome.”
The study was published online July 22 in the Journal of the National Cancer Institute.
The study period ran from 2018 to 2019, and looked at articles posted on social media platforms Facebook, Reddit, Twitter, or Pinterest. Popularity was measured by engagement with readers, such as upvotes, comments, reactions, and shares.
Some of the articles came from long-established news entities such as CBS News, The New York Times, and medical journals, while others came from fleeting crowdfunding web pages and fledging nontraditional news sites.
One example of popular and harmful misinformation highlighted by Dr. Johnson in an interview was titled, “44-Year-Old Mother Claims CBD Oil Cured Her of Breast Cancer within 5 Months.” Posted on truththeory.com in February 2018, the article is tagged as “opinion” by the publisher and in turn links to another news story about the same woman in the UK’s Daily Mail newspaper.
The ideas and claims in such articles can be very influential, Jennifer L. Lycette, MD, suggested in a recent blog post.
“After 18 years as a cancer doctor, it sadly doesn’t come as a surprise anymore when a patient declines treatment recommendations and instead opts for ‘alternative’ treatment,” she wrote.
Sometimes, misinformation is not sensational but is still effective via clever wording and presentation, observed Brian G. Southwell, PhD, of Duke University, Durham, N.C., who has studied patients and misinformation.
“It isn’t the falsehood that is somehow magically attractive, per se, but the way that misinformation is often framed that can make it attractive,” he said in an interview.
Dr. Southwell recommends that clinicians be proactive about medical misinformation.
“Rather than expect patients to raise concerns without prompting, health care providers should invite conversations about potential misinformation with their patients,” he wrote in a recent essay in the American Journal of Public Health.
In short, ask patients what they know about the treatment of their cancer, he suggests.
“Patients don’t typically know that the misinformation they are encountering is misinformation,” said Dr. Southwell. “Approaching patients with compassion and empathy is a good first step.”
Study details
For the study, reported by Johnson et al., two National Comprehensive Cancer Network panel members were selected as content experts for each of the four cancers and were tasked with reviewing the primary medical claims in each article. The experts then completed a set of ratings to arrive at the proportion of misinformation and potential for harm in each article.
Of the 200 articles, 41.5% were from nontraditional news (digital only), 37.5% were from traditional news sources (online versions of print and/or broadcast media), 17% were from medical journals, 3% were from a crowdfunding site, and 1% were from personal blogs.
This expert review concluded that nearly one-third of the articles contained misinformation, as noted above. The misinformation was described as misleading (title not supported by text or statistics/data do not support conclusion, 28.8%), strength of the evidence mischaracterized (weak evidence portrayed as strong or vice versa, 27.7%) and unproven therapies (not studied or insufficient evidence, 26.7%).
Notably, the median number of engagements, such as likes on Twitter, for articles with misinformation was greater than that of factual articles (median, 2,300 vs. 1,600; P = .05).
In total, 30.5% of all 200 articles contained harmful information. This was described as harmful inaction (could lead to delay or not seeking medical attention for treatable/curable condition, 31.0%), economic harm (out-of-pocket financial costs associated with treatment/travel, 27.7%), harmful action (potentially toxic effects of the suggested test/treatment, 17.0%), and harmful interactions (known/unknown medical interactions with curative therapies, 16.2%).
The median number of engagements for articles with harmful information was statistically significantly greater than that of articles with correct information (median, 2,300 vs. 1,500; P = .007).
A limitation of the study is that it included only the most popular English language cancer articles.
This study was funded in part by the Huntsman Cancer Institute. Dr. Johnson, Dr. Lycette, and Dr. Southwell have disclosed no relevant financial relationships. Some study authors have ties to the pharmaceutical industry.
A version of this article first appeared on Medscape.com.
Bone drugs for prostate cancer may result in survival benefit
Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.
The findings were published online July 22, 2021, in JAMA Network Open.
All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.
While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.
So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.
Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).
There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.
Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).
Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).
Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.”
Importance of bone-targeted drugs
“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.
Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.
So, why aren’t more men receiving BRIs?
“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.
“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.
As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).
“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.
“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
Costly vs. inexpensive BRI
The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.
The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”
The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.
In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.
International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.
The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.
In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.
There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.
Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.
The findings were published online July 22, 2021, in JAMA Network Open.
All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.
While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.
So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.
Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).
There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.
Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).
Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).
Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.”
Importance of bone-targeted drugs
“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.
Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.
So, why aren’t more men receiving BRIs?
“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.
“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.
As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).
“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.
“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
Costly vs. inexpensive BRI
The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.
The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”
The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.
In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.
International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.
The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.
In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.
There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.
Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from a retrospective study show that the addition of bone resorption inhibitors (BRIs), including zoledronic acid and denosumab (Xgeva), to abiraterone plus prednisolone was associated with significantly longer overall survival (OS). The median OS was increased by nearly 9 months among recipients, compared with men who didn’t receive these drugs in this setting.
The findings were published online July 22, 2021, in JAMA Network Open.
All men with prostate cancer should receive BRIs “as the disease reaches the castration resistance with bone metastases stage, as recommended by the international guidelines,” lead author Edoardo Francini, MD, PhD, of the University of Florence (Italy) said in a comment.
While there is no evidence that BRIs – when used alone – may improve survival in metastatic castration-resistant prostate cancer (mCRPC) with bone involvement, there has been a “suggestion” of a survival benefit with BRIs when combined with other anticancer therapies in this setting, say the authors.
So Dr. Francini and a team of international coinvestigators looked at the medical records of men with mCRPC and bone metastases treated at eight institutions in Canada, Europe, and the United States and focused on patients who received abiraterone acetate (with prednisone) because it is the most common first-line therapy in this setting.
Patients were classified by receipt versus nonreceipt of concomitant BRIs and subclassified by volume of disease (high or low volume).
There were two cohorts in the study population: 529 men (71.0%) who received abiraterone alone and 216 men (29.0%) who received abiraterone plus BRIs. The median follow-up was 23.5 months.
Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone alone cohort (31.8 vs. 23.0 months; hazard ratio, 0.65; P < .001).
Notably, the OS benefit in the BRI cohort was greater for patients with high-volume versus low-volume disease (33.6 vs. 19.7 months; HR, 0.51; P < .001).
Dr. Francini hopes the new study results can effect change. “Hopefully, clinicians will be more inclined to use bone resorption inhibitors in combination with abiraterone acetate plus prednisone as soon as the disease reaches the castration-resistance with bone metastases stage, as recommended by the international guidelines.”
Importance of bone-targeted drugs
“This study highlights the importance of bone-targeted therapy in current practice for men with mCRPC and bone metastases,” Samuel Takvorian, MD, and Naomi Haas, MD, of the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.
But the study also reveals that work needs to be done to get clinicians to prescribe BRIs, they said, and that clinical pathways and behavioral “nudges” could help promote adoption.
Most (71%) of the men in this study did not get bone protective drug therapy, they pointed out, even though they were being treated at major hospital systems.
So, why aren’t more men receiving BRIs?
“I think this is less likely due to poor communication from professional societies (the guidelines are clear) and more likely due to bone health being low on the list of priorities for these patients and clinician uncertainty and/or lack of appreciation of the clinical benefit of these agents,” Dr. Takvorian said in an interview.
“When prostate cancer progresses to the castration-resistant phase, clinicians (and patients) rightfully are focused on the next cancer-directed therapy. However, this may be at the expense of supportive care, like bone agents, which often gets short shrift,” he added.
As would be expected, the men who were taking BRIs had a significantly shorter time to first skeletal-related events (SREs), compared with those who were not (32.4 vs. 42.7 months; HR, 1.27; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; P < .001).
“These SREs collectively represent a clinically meaningful outcome that is often measured in clinical trials,” the editorialists observed. In the current study, SREs were comprised of pathological fractures, spinal cord compression, or the need for surgery or radiotherapy to bone.
“Up to one-half of men with mCRPC, the advanced and often fatal stage of disease, experience SREs, which are associated with considerable morbidity, decreased survival, and increased health care utilization and costs,” they wrote.
Costly vs. inexpensive BRI
The study found no difference in the OS benefit between the different BRIs used, that is, between that seen with zoledronic acid versus denosumab.
The editorialists suggested that this finding is important, even though it “must be considered preliminary given the limitations of a retrospective study.” These results add “to data suggesting that these agents are comparably beneficial; thus, decisions between them should focus on clinical factors, such as kidney function, patient preference, and cost.”
The two agents differ mechanistically, they added, with zoledronic acid preferentially inhibiting osteoclast proliferation and denosumab inhibiting an important factor in osteoclast maturation.
In terms of having differentiating characteristics, the editorialists say that zoledronic acid is “more often associated with acute phase reactions and required monitoring of kidney function” while “denosumab conferred a higher risk of hypocalcemia.” Rates of osteonecrosis of the jaw are comparable.
International guidelines endorse the use of either agent for the treatment of men with mCRPC. But “some argue that the marginal benefit of denosumab must be weighed against its dramatically higher cost (the annual cost of zoledronic acid is approximately $140 vs. $29,000 for denosumab),” the editorialists said.
The dramatically higher cost of denosumab versus zoledronic acid has also been noted by other oncologists treating patients with other cancers, including multiple myeloma.
In addition to drug costs, there is another issue at stake: the prescribing oncologist is reimbursed by Medicare Part D at 6% for whichever drug is chosen, which represents a “financial conflict” for oncologists, said Vincent Rajkumar, MD, professor of medicine and a hematologist/oncologist at the Mayo Clinic, Rochester, Minn.
There is also a difference in how the drugs are administered, which may influence patient preference, the myeloma experts noted. Zoledronic acid is given intravenously every 3 months and requires a 15-minute infusion at a center, while denosumab needs to be given more frequently (every month) but is administered by subcutaneous injection.
Dr. Francini reported receiving grants from Roche Italia and personal fees for research travel from Janssen-Cilag outside the submitted work. A number of other authors disclosed financial ties to Janssen or Amgen, makers of abiraterone and denosumab, respectively. The editorialists reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The robot comes to mastectomy, but cancer outcomes data not attached
The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.
The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.
The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.
In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.
Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.
However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.
Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.
Importantly, none of the studies is a randomized trial; all have single arms.
That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.
“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.
As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”
In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
Not looking at the right outcomes
“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.
“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.
The current U.S. trials are “totally inappropriate,” he said.
Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.
“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.
What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.
Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
Safety concerns with robotic mastectomy
Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.
That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.
But therein also lies a safety concern, she asserted.
The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”
Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”
Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.
Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
In defense of single-arm trials
“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.
Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.
The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.
The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.
“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.
But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”
Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
Prophylactic use is also a cancer surgery
Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).
The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.
Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.
“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.
Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.
Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.
It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.
“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.
The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
Surgeons only get one body
Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.
However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.
Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.
One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.
Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.
“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.
When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”
Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.
The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.
The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.
In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.
Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.
However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.
Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.
Importantly, none of the studies is a randomized trial; all have single arms.
That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.
“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.
As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”
In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
Not looking at the right outcomes
“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.
“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.
The current U.S. trials are “totally inappropriate,” he said.
Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.
“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.
What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.
Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
Safety concerns with robotic mastectomy
Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.
That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.
But therein also lies a safety concern, she asserted.
The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”
Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”
Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.
Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
In defense of single-arm trials
“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.
Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.
The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.
The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.
“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.
But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”
Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
Prophylactic use is also a cancer surgery
Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).
The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.
Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.
“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.
Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.
Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.
It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.
“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.
The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
Surgeons only get one body
Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.
However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.
Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.
One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.
Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.
“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.
When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”
Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.
The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.
The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.
In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.
Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.
However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.
Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.
Importantly, none of the studies is a randomized trial; all have single arms.
That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.
“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.
As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”
In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
Not looking at the right outcomes
“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.
“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.
The current U.S. trials are “totally inappropriate,” he said.
Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.
“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.
What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.
Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
Safety concerns with robotic mastectomy
Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.
That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.
But therein also lies a safety concern, she asserted.
The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”
Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”
Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.
Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
In defense of single-arm trials
“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.
Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.
The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.
The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.
“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.
But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”
Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
Prophylactic use is also a cancer surgery
Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).
The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.
Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.
“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.
Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.
Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.
It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.
“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.
The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
Surgeons only get one body
Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.
However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.
Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.
One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.
Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.
“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.
When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”
Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Freezing breast cancer to death avoids surgery: Why not further along?
In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.
Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.
But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.
So why is this approach still experimental for breast cancer?
“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.
“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
New clinical data
Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.
Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.
The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.
It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.
The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.
These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.
The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.
Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.
“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.
The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.
Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”
There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.
Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.
But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
Not likely to show superiority
The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.
The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”
That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.
There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.
Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.
Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.
“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.
“The patients in this study were exceedingly low risk,” she emphasized.
“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”
Thus, it will be difficult to show that cryoablation is superior to surgery, she said.
“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
The surgical mindset and breast cancer
Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.
“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.
“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.
“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.
But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.
The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”
As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.
Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.
However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).
Dr. Attai hopes the field is ready for the nonsurgical approach.
“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.
Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.
Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.
But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.
So why is this approach still experimental for breast cancer?
“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.
“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
New clinical data
Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.
Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.
The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.
It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.
The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.
These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.
The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.
Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.
“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.
The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.
Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”
There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.
Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.
But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
Not likely to show superiority
The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.
The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”
That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.
There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.
Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.
Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.
“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.
“The patients in this study were exceedingly low risk,” she emphasized.
“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”
Thus, it will be difficult to show that cryoablation is superior to surgery, she said.
“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
The surgical mindset and breast cancer
Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.
“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.
“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.
“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.
But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.
The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”
As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.
Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.
However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).
Dr. Attai hopes the field is ready for the nonsurgical approach.
“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.
Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.
Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.
But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.
So why is this approach still experimental for breast cancer?
“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.
“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
New clinical data
Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.
Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.
The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.
It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.
The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.
These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.
The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.
Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.
“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.
The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.
Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”
There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.
Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.
But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
Not likely to show superiority
The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.
The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”
That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.
There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.
Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.
Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.
“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.
“The patients in this study were exceedingly low risk,” she emphasized.
“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”
Thus, it will be difficult to show that cryoablation is superior to surgery, she said.
“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
The surgical mindset and breast cancer
Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.
“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.
“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.
“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.
But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.
The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”
As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.
Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.
However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).
Dr. Attai hopes the field is ready for the nonsurgical approach.
“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.
Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In the previous year, 70% of oncologists reported sexual harassment
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA OKs nivolumab after surgery for esophageal or GEJ cancer: Practice-changing use of immunotherapy
The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.
The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.
The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.
This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.
“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.
In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.
All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.
For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).
The median follow-up was 24.4 months.
Disease-free survival favored nivolumab across multiple preplanned subgroups.
However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).
There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).
There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).
No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.
Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).
Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.
Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”
When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.
Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.
Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.
In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.
The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.
The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.
This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.
“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.
In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.
All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.
For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).
The median follow-up was 24.4 months.
Disease-free survival favored nivolumab across multiple preplanned subgroups.
However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).
There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).
There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).
No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.
Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).
Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.
Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”
When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.
Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.
Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.
In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.
The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.
The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.
This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.
“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.
In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.
All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.
For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).
The median follow-up was 24.4 months.
Disease-free survival favored nivolumab across multiple preplanned subgroups.
However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).
There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).
There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).
No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.
Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).
Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.
Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”
When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.
Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.
Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.
In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.
A version of this article first appeared on Medscape.com.
FDA okays upfront pembro for advanced HER2+ gastric cancer
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
FDA approves new immunotherapy for endometrial cancer
Use limited to patients with biomarker
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.
Use limited to patients with biomarker
Use limited to patients with biomarker
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.
Usage of the new checkpoint inhibitor is limited to patients who have progressed on or following prior treatment with a platinum-containing chemotherapy. Eligibility must also be determined by an FDA-approved test for the dMMR biomarker. Approximately 25%-30% of patients with advanced endometrial cancer have dMMR tumors, according to the FDA.
The approval is “evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
He explained that the immunotherapy was “specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response.”
The new drug also addresses an unmet medical need, as there are limited therapeutic options in this setting following frontline standard treatment with a platinum-containing chemotherapy.
The approval is based on safety and efficacy data from a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab, 42.3% had a response. For 93% of that group, the response lasted 6 months or longer.
The drug’s maker, GlaxoSmithKline, is currently conducting additional, larger trials in more patients with dMMR endometrial tumors to verify and further describe clinical benefits.
Common side effects of dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Like other checkpoint inhibitors, the new drug can cause immune-mediated side effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is contraindicated in women who are pregnant or breastfeeding because it may cause harm to a developing fetus or newborn baby.
The FDA approval comes a month after the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting conditional marketing authorization for dostarlimab for use as monotherapy in this same patient group.
In the United States, dostarlimab received Priority Review designation and Breakthrough Therapy designation for this indication.
A version of this article first appeared on Medscape.com.