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Fifth COVID shot recommended for patients with cancer
The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.
A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.
The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved.
“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.
The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.
The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.
The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.
“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.
A version of this article first appeared on Medscape.com.
The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.
A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.
The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved.
“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.
The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.
The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.
The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.
“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.
A version of this article first appeared on Medscape.com.
The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.
A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.
The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved.
“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.
The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.
The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.
The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.
“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.
A version of this article first appeared on Medscape.com.
ctDNA unreliable for detecting CRC recurrence after surgery
conclude the authors of a review of 48 patients at the City of Hope Comprehensive Cancer Center, outside of Los Angeles.
Two ctDNA tests that are used for this purpose are already marketed in the United States: Signatera (Natera) and Reveal (Guardant Health).
This use of ctDNA has been catching on with oncologists in the United States, noted the authors. Such use is based on the premise that the test catches recurrences earlier than imaging and carcinoembryonic antigen (CEA) monitoring, which is the standard approach recommended by the National Comprehensive Cancer Network and the European Society of Medical Oncology.
The review was published online on March 8, 2022, in JAMA Network Open.
The review included 48 patients with stage II-IV colorectal cancer whose disease was in remission after curative-intent surgery. They were followed with CT imaging and CEA, as per NCCN guidelines, and with the Signatera ctDNA test from Natera.
The authors, led by Marwan Fakih, MD, a gastrointestinal oncologist at City of Hope, concluded that ctDNA “provides no definitive advantage compared with standard imaging and CEA measurement in the surveillance of patients with resected colorectal cancer.”
In fact, they suggested that clinicians “have taken a giant leap of faith by endorsing ctDNA assays as predictive and prognostic.” They noted that ongoing phase 3 trials are investigating the deescalation or even elimination of adjuvant chemotherapy, based on negative ctDNA results, as, for example, in a study reported recently at the 2022 Gastrointestinal Cancers Symposium.
“For now, ctDNA can be considered, if ... at all, as a complement to the standard approach recommended by the NCCN, but one must be cognizant of its limitations,” Dr. Fakih commented in a press release.
Asked for comment, Natera countered that its test is backed by “over a dozen peer-reviewed studies, with over 3,000 patients studied across multiple cancer types.” About the review, the company said that “small clinical experience studies are subject to limitations and variability.” It also emphasized that the company “has always supported the use of Signatera in combination with imaging,” not as a replacement.
Study details
Among the 49 patients included in the review, 15 experienced recurrence, but only eight of these patients had concurrent positive results on ctDNA.
Five of eight patients with lung recurrences were identified by CT imaging before the ctDNA test was positive or had persistently negative ctDNA results.
“A negative ctDNA finding is common in the setting of low-volume metastatic disease, especially in metastatic disease of the lung,” the investigators said.
Imaging plus CEA identified recurrences before ctDNA in seven cases, and it did so concurrently with ctDNA in four cases, yielding a sensitivity of 73.3% for recurrence versus 53.3% for ctDNA, but the finding wasn’t statistically significant, owing to the small number of patients.
The ctDNA test did identify five patients before imaging, but the investigators said it was “unlikely” that the finding changed treatment.
One patient had multiple lung metastases, and two patients had diffuse retroperitoneal disease, so none of the three were candidates for curative-intent surgery.
The other two patients did undergo surgery, but the investigators said they “would have arguably experienced a similar intervention if followed up by standard surveillance.”
The two retroperitoneal cases were positive on ctDNA for well over a year before recurrences showed up on imaging, which raises another point, commented the author of an accompanying commentary.
Discovering minimal residual disease (MRD) by “ctDNA before the site of recurrence can be localized” for surgery “does not open the window of opportunity. Instead ... patients receive bad news that is not actionable” and “might be harmed” by “learning of inevitable cancer recurrence with nothing to do but wait,” Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, wrote in the commentary.
“If ctDNA can indeed detect MRD sooner than imaging, then interventional trials with molecular response as an end point are warranted to determine whether ctDNA detection is an actionable finding,” he said.
Dr. Fakih and associates noted that much of “the enthusiasm around these assays, particularly Signatera, was generated by a large observational surveillance trial” in Denmark that found that ctDNA identified disease recurrence an average of 8.7 months before CT imaging.
However, imaging was performed at 1 and 3 years, which they say is “considered substandard” in the United States and many European countries.
There was no funding for the review. Dr. Fakih has numerous ties with industry, including being a speaker for Guardant360; parent company Guardant Health markets a rival ctDNA test, Guardant Reveal. Dr. Fakih is also a speaker for Amgen and is an adviser for and/or receives institutional grants from Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others. Dr. Venook has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
conclude the authors of a review of 48 patients at the City of Hope Comprehensive Cancer Center, outside of Los Angeles.
Two ctDNA tests that are used for this purpose are already marketed in the United States: Signatera (Natera) and Reveal (Guardant Health).
This use of ctDNA has been catching on with oncologists in the United States, noted the authors. Such use is based on the premise that the test catches recurrences earlier than imaging and carcinoembryonic antigen (CEA) monitoring, which is the standard approach recommended by the National Comprehensive Cancer Network and the European Society of Medical Oncology.
The review was published online on March 8, 2022, in JAMA Network Open.
The review included 48 patients with stage II-IV colorectal cancer whose disease was in remission after curative-intent surgery. They were followed with CT imaging and CEA, as per NCCN guidelines, and with the Signatera ctDNA test from Natera.
The authors, led by Marwan Fakih, MD, a gastrointestinal oncologist at City of Hope, concluded that ctDNA “provides no definitive advantage compared with standard imaging and CEA measurement in the surveillance of patients with resected colorectal cancer.”
In fact, they suggested that clinicians “have taken a giant leap of faith by endorsing ctDNA assays as predictive and prognostic.” They noted that ongoing phase 3 trials are investigating the deescalation or even elimination of adjuvant chemotherapy, based on negative ctDNA results, as, for example, in a study reported recently at the 2022 Gastrointestinal Cancers Symposium.
“For now, ctDNA can be considered, if ... at all, as a complement to the standard approach recommended by the NCCN, but one must be cognizant of its limitations,” Dr. Fakih commented in a press release.
Asked for comment, Natera countered that its test is backed by “over a dozen peer-reviewed studies, with over 3,000 patients studied across multiple cancer types.” About the review, the company said that “small clinical experience studies are subject to limitations and variability.” It also emphasized that the company “has always supported the use of Signatera in combination with imaging,” not as a replacement.
Study details
Among the 49 patients included in the review, 15 experienced recurrence, but only eight of these patients had concurrent positive results on ctDNA.
Five of eight patients with lung recurrences were identified by CT imaging before the ctDNA test was positive or had persistently negative ctDNA results.
“A negative ctDNA finding is common in the setting of low-volume metastatic disease, especially in metastatic disease of the lung,” the investigators said.
Imaging plus CEA identified recurrences before ctDNA in seven cases, and it did so concurrently with ctDNA in four cases, yielding a sensitivity of 73.3% for recurrence versus 53.3% for ctDNA, but the finding wasn’t statistically significant, owing to the small number of patients.
The ctDNA test did identify five patients before imaging, but the investigators said it was “unlikely” that the finding changed treatment.
One patient had multiple lung metastases, and two patients had diffuse retroperitoneal disease, so none of the three were candidates for curative-intent surgery.
The other two patients did undergo surgery, but the investigators said they “would have arguably experienced a similar intervention if followed up by standard surveillance.”
The two retroperitoneal cases were positive on ctDNA for well over a year before recurrences showed up on imaging, which raises another point, commented the author of an accompanying commentary.
Discovering minimal residual disease (MRD) by “ctDNA before the site of recurrence can be localized” for surgery “does not open the window of opportunity. Instead ... patients receive bad news that is not actionable” and “might be harmed” by “learning of inevitable cancer recurrence with nothing to do but wait,” Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, wrote in the commentary.
“If ctDNA can indeed detect MRD sooner than imaging, then interventional trials with molecular response as an end point are warranted to determine whether ctDNA detection is an actionable finding,” he said.
Dr. Fakih and associates noted that much of “the enthusiasm around these assays, particularly Signatera, was generated by a large observational surveillance trial” in Denmark that found that ctDNA identified disease recurrence an average of 8.7 months before CT imaging.
However, imaging was performed at 1 and 3 years, which they say is “considered substandard” in the United States and many European countries.
There was no funding for the review. Dr. Fakih has numerous ties with industry, including being a speaker for Guardant360; parent company Guardant Health markets a rival ctDNA test, Guardant Reveal. Dr. Fakih is also a speaker for Amgen and is an adviser for and/or receives institutional grants from Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others. Dr. Venook has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
conclude the authors of a review of 48 patients at the City of Hope Comprehensive Cancer Center, outside of Los Angeles.
Two ctDNA tests that are used for this purpose are already marketed in the United States: Signatera (Natera) and Reveal (Guardant Health).
This use of ctDNA has been catching on with oncologists in the United States, noted the authors. Such use is based on the premise that the test catches recurrences earlier than imaging and carcinoembryonic antigen (CEA) monitoring, which is the standard approach recommended by the National Comprehensive Cancer Network and the European Society of Medical Oncology.
The review was published online on March 8, 2022, in JAMA Network Open.
The review included 48 patients with stage II-IV colorectal cancer whose disease was in remission after curative-intent surgery. They were followed with CT imaging and CEA, as per NCCN guidelines, and with the Signatera ctDNA test from Natera.
The authors, led by Marwan Fakih, MD, a gastrointestinal oncologist at City of Hope, concluded that ctDNA “provides no definitive advantage compared with standard imaging and CEA measurement in the surveillance of patients with resected colorectal cancer.”
In fact, they suggested that clinicians “have taken a giant leap of faith by endorsing ctDNA assays as predictive and prognostic.” They noted that ongoing phase 3 trials are investigating the deescalation or even elimination of adjuvant chemotherapy, based on negative ctDNA results, as, for example, in a study reported recently at the 2022 Gastrointestinal Cancers Symposium.
“For now, ctDNA can be considered, if ... at all, as a complement to the standard approach recommended by the NCCN, but one must be cognizant of its limitations,” Dr. Fakih commented in a press release.
Asked for comment, Natera countered that its test is backed by “over a dozen peer-reviewed studies, with over 3,000 patients studied across multiple cancer types.” About the review, the company said that “small clinical experience studies are subject to limitations and variability.” It also emphasized that the company “has always supported the use of Signatera in combination with imaging,” not as a replacement.
Study details
Among the 49 patients included in the review, 15 experienced recurrence, but only eight of these patients had concurrent positive results on ctDNA.
Five of eight patients with lung recurrences were identified by CT imaging before the ctDNA test was positive or had persistently negative ctDNA results.
“A negative ctDNA finding is common in the setting of low-volume metastatic disease, especially in metastatic disease of the lung,” the investigators said.
Imaging plus CEA identified recurrences before ctDNA in seven cases, and it did so concurrently with ctDNA in four cases, yielding a sensitivity of 73.3% for recurrence versus 53.3% for ctDNA, but the finding wasn’t statistically significant, owing to the small number of patients.
The ctDNA test did identify five patients before imaging, but the investigators said it was “unlikely” that the finding changed treatment.
One patient had multiple lung metastases, and two patients had diffuse retroperitoneal disease, so none of the three were candidates for curative-intent surgery.
The other two patients did undergo surgery, but the investigators said they “would have arguably experienced a similar intervention if followed up by standard surveillance.”
The two retroperitoneal cases were positive on ctDNA for well over a year before recurrences showed up on imaging, which raises another point, commented the author of an accompanying commentary.
Discovering minimal residual disease (MRD) by “ctDNA before the site of recurrence can be localized” for surgery “does not open the window of opportunity. Instead ... patients receive bad news that is not actionable” and “might be harmed” by “learning of inevitable cancer recurrence with nothing to do but wait,” Alan Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco, wrote in the commentary.
“If ctDNA can indeed detect MRD sooner than imaging, then interventional trials with molecular response as an end point are warranted to determine whether ctDNA detection is an actionable finding,” he said.
Dr. Fakih and associates noted that much of “the enthusiasm around these assays, particularly Signatera, was generated by a large observational surveillance trial” in Denmark that found that ctDNA identified disease recurrence an average of 8.7 months before CT imaging.
However, imaging was performed at 1 and 3 years, which they say is “considered substandard” in the United States and many European countries.
There was no funding for the review. Dr. Fakih has numerous ties with industry, including being a speaker for Guardant360; parent company Guardant Health markets a rival ctDNA test, Guardant Reveal. Dr. Fakih is also a speaker for Amgen and is an adviser for and/or receives institutional grants from Amgen, GlaxoSmithKline, Bristol-Myers Squibb, and others. Dr. Venook has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
FDA approves new immunotherapy combo for metastatic melanoma
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
As predicted: jump in metastatic prostate cancer diagnoses
men with the prostate-specific antigen (PSA), shows a report published online in JAMA Network Open.
It was a consequence that many experts in prostate cancer predicted at the time the recommendation was made – initially in 2008 against routine screening in men older than 75 years, then in all men in 2012.
The thinking was that the harms of screening all men – leading to unnecessary prostatectomies and other treatments in many men – outweighed the benefits of catching early high-risk disease in fewer men. Screening rates plummeted as a result.
But experts in prostate cancer warned that the move, while reducing overdiagnosis and overtreatment, would have the unfortunate consequence of underdiagnosis and, consequently, nondetection of the cases of prostate cancer that would spread.
The new findings are the latest to suggest that this is, in fact, what happened, and echo similar findings previously reported by this news organization.
For this study, investigators at the University of Southern California, Los Angeles, analyzed the incidence of metastatic prostate cancer (mPCa) in the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2018, with 2018 being the latest data available.
SEER captures about 28% of the U.S. population and recorded almost 50,000 new mPCa cases over the period.
Among men 45-75 years old, the incidence of mPCa increased 41% from when USPSTF recommended against screening through 2018, which translated to an annual percentage change (APC) of 5.3%.
Among men 75 years and older, mPCa rates jumped 43% through 2018, an APC of 6.5%.
The researchers did not find an increase in deaths from prostate cancer, but given the 5-7 years median survival, it might be too early to tell.
“The observation of a rising incidence of mPCa in itself does not imply that screening practices should be changed. The overall risk versus benefit of PSA-based screening is extremely complex and must take into account various other factors that impact the overall health of the community,” say investigators, led by Mihir Desai, MD, a clinical urology professor at USC.
However, screening practices have already changed. The USPSTF withdrew its objections to screening in 2018 and instead recommended personalized decisionmaking for men 55-69 years old, citing new evidence that screening prevents metastatic disease and reduces PCa mortality more than previously recognized, Richard Hoffman, MD, MPH, an internal medicine professor at the University of Iowa, Iowa City, said in an accompanying editorial.
The study’s trends in mPCa “might be transitory because the screening guidelines have” changed, Dr. Hoffman writes.
For now, clinicians should “consistently address screening with men who are healthy enough to benefit” from catching dangerous tumors early and engage them “in shared decisionmaking discussions to” strike the right balance between minimizing overdiagnosis and catching high-risk tumors before they spread, he said.
Easier said than done, but the field is advancing. Active surveillance, instead of surgery, for what seem to be low-risk tumors is one step in the right direction, Dr. Hoffman commented.
No external funding was reported. Dr. Desai is a consultant for Procept Biorobotics and Auris Surgical. Dr. Hoffman reported royalties from UpToDate and fees from law firms as an expert witness on prostate cancer screening cases.
A version of this article first appeared on Medscape.com.
men with the prostate-specific antigen (PSA), shows a report published online in JAMA Network Open.
It was a consequence that many experts in prostate cancer predicted at the time the recommendation was made – initially in 2008 against routine screening in men older than 75 years, then in all men in 2012.
The thinking was that the harms of screening all men – leading to unnecessary prostatectomies and other treatments in many men – outweighed the benefits of catching early high-risk disease in fewer men. Screening rates plummeted as a result.
But experts in prostate cancer warned that the move, while reducing overdiagnosis and overtreatment, would have the unfortunate consequence of underdiagnosis and, consequently, nondetection of the cases of prostate cancer that would spread.
The new findings are the latest to suggest that this is, in fact, what happened, and echo similar findings previously reported by this news organization.
For this study, investigators at the University of Southern California, Los Angeles, analyzed the incidence of metastatic prostate cancer (mPCa) in the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2018, with 2018 being the latest data available.
SEER captures about 28% of the U.S. population and recorded almost 50,000 new mPCa cases over the period.
Among men 45-75 years old, the incidence of mPCa increased 41% from when USPSTF recommended against screening through 2018, which translated to an annual percentage change (APC) of 5.3%.
Among men 75 years and older, mPCa rates jumped 43% through 2018, an APC of 6.5%.
The researchers did not find an increase in deaths from prostate cancer, but given the 5-7 years median survival, it might be too early to tell.
“The observation of a rising incidence of mPCa in itself does not imply that screening practices should be changed. The overall risk versus benefit of PSA-based screening is extremely complex and must take into account various other factors that impact the overall health of the community,” say investigators, led by Mihir Desai, MD, a clinical urology professor at USC.
However, screening practices have already changed. The USPSTF withdrew its objections to screening in 2018 and instead recommended personalized decisionmaking for men 55-69 years old, citing new evidence that screening prevents metastatic disease and reduces PCa mortality more than previously recognized, Richard Hoffman, MD, MPH, an internal medicine professor at the University of Iowa, Iowa City, said in an accompanying editorial.
The study’s trends in mPCa “might be transitory because the screening guidelines have” changed, Dr. Hoffman writes.
For now, clinicians should “consistently address screening with men who are healthy enough to benefit” from catching dangerous tumors early and engage them “in shared decisionmaking discussions to” strike the right balance between minimizing overdiagnosis and catching high-risk tumors before they spread, he said.
Easier said than done, but the field is advancing. Active surveillance, instead of surgery, for what seem to be low-risk tumors is one step in the right direction, Dr. Hoffman commented.
No external funding was reported. Dr. Desai is a consultant for Procept Biorobotics and Auris Surgical. Dr. Hoffman reported royalties from UpToDate and fees from law firms as an expert witness on prostate cancer screening cases.
A version of this article first appeared on Medscape.com.
men with the prostate-specific antigen (PSA), shows a report published online in JAMA Network Open.
It was a consequence that many experts in prostate cancer predicted at the time the recommendation was made – initially in 2008 against routine screening in men older than 75 years, then in all men in 2012.
The thinking was that the harms of screening all men – leading to unnecessary prostatectomies and other treatments in many men – outweighed the benefits of catching early high-risk disease in fewer men. Screening rates plummeted as a result.
But experts in prostate cancer warned that the move, while reducing overdiagnosis and overtreatment, would have the unfortunate consequence of underdiagnosis and, consequently, nondetection of the cases of prostate cancer that would spread.
The new findings are the latest to suggest that this is, in fact, what happened, and echo similar findings previously reported by this news organization.
For this study, investigators at the University of Southern California, Los Angeles, analyzed the incidence of metastatic prostate cancer (mPCa) in the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2018, with 2018 being the latest data available.
SEER captures about 28% of the U.S. population and recorded almost 50,000 new mPCa cases over the period.
Among men 45-75 years old, the incidence of mPCa increased 41% from when USPSTF recommended against screening through 2018, which translated to an annual percentage change (APC) of 5.3%.
Among men 75 years and older, mPCa rates jumped 43% through 2018, an APC of 6.5%.
The researchers did not find an increase in deaths from prostate cancer, but given the 5-7 years median survival, it might be too early to tell.
“The observation of a rising incidence of mPCa in itself does not imply that screening practices should be changed. The overall risk versus benefit of PSA-based screening is extremely complex and must take into account various other factors that impact the overall health of the community,” say investigators, led by Mihir Desai, MD, a clinical urology professor at USC.
However, screening practices have already changed. The USPSTF withdrew its objections to screening in 2018 and instead recommended personalized decisionmaking for men 55-69 years old, citing new evidence that screening prevents metastatic disease and reduces PCa mortality more than previously recognized, Richard Hoffman, MD, MPH, an internal medicine professor at the University of Iowa, Iowa City, said in an accompanying editorial.
The study’s trends in mPCa “might be transitory because the screening guidelines have” changed, Dr. Hoffman writes.
For now, clinicians should “consistently address screening with men who are healthy enough to benefit” from catching dangerous tumors early and engage them “in shared decisionmaking discussions to” strike the right balance between minimizing overdiagnosis and catching high-risk tumors before they spread, he said.
Easier said than done, but the field is advancing. Active surveillance, instead of surgery, for what seem to be low-risk tumors is one step in the right direction, Dr. Hoffman commented.
No external funding was reported. Dr. Desai is a consultant for Procept Biorobotics and Auris Surgical. Dr. Hoffman reported royalties from UpToDate and fees from law firms as an expert witness on prostate cancer screening cases.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Wake Forest Cancer Center director fired, advisory board resigns
and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.
The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.
The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.
The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.
Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.
A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”
Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.
The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”
Dr. Pasche was fired a day later.
The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”
“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.
“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.
The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”
The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.
The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”
A version of this article first appeared on Medscape.com.
and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.
The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.
The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.
The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.
Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.
A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”
Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.
The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”
Dr. Pasche was fired a day later.
The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”
“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.
“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.
The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”
The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.
The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”
A version of this article first appeared on Medscape.com.
and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.
The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.
The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.
The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.
Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.
A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”
Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.
The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”
Dr. Pasche was fired a day later.
The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”
“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.
“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.
The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”
The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.
The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”
A version of this article first appeared on Medscape.com.
Active surveillance or maintenance after chemo induction in metastatic CRC?
Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?
In a recent trial designed to explore this question,
The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.
But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.
The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.
Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.
Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”
Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.
In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.
The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).
Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).
Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.
With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.
A viable option
The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.
According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”
In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.
“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.
An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.
“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial.
Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.
The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.
“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
Caveats to the study
A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.
In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.
In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.
“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.
In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.
Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.
Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”
The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.
A version of this article first appeared on Medscape.com.
Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?
In a recent trial designed to explore this question,
The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.
But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.
The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.
Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.
Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”
Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.
In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.
The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).
Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).
Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.
With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.
A viable option
The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.
According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”
In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.
“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.
An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.
“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial.
Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.
The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.
“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
Caveats to the study
A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.
In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.
In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.
“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.
In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.
Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.
Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”
The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.
A version of this article first appeared on Medscape.com.
Should patients with metastatic colorectal cancer (CRC) who respond to first-line treatment receive maintenance therapy, or are they better off on active surveillance?
In a recent trial designed to explore this question,
The researchers found that patients with metastatic CRC randomized to maintenance therapy with oral capecitabine (Xeloda) showed improved progression-free survival (PFS), compared with those being actively monitored – 3.88 versus 1.87 months.
But that benefit came at a cost. Patients on capecitabine experienced much worse toxicity and showed no overall survival benefit – 14.8 months in the capecitabine arm versus 15.2 in the surveillance arm.
The FOCUS4-N trial supports “the use of treatment breaks as safe management alternatives for patients” after induction, lead author Richard Adams, MD, an oncology professor at Cardiff University, Wales, and colleagues conclude in a study published in the Journal of Clinical Oncology.
Current treatment standards either require or recommend that patients with metastatic CRC receive maintenance therapy after induction chemotherapy, at least until they progress or experience excessive toxicity.
Although maintenance strategies have typically demonstrated a PFS benefit, that advantage may come at “the expense of ongoing ... toxicity.”
Dr. Adams and colleagues wanted to explore how patients would fare on an oral maintenance therapy with capecitabine, compared with active surveillance.
In the trial, researchers randomly assigned 254 patients who had responded to first-line therapy or had stable disease to either capecitabine (n = 127) or active monitoring (n = 127). Subjects were treated at 88 hospitals in the United Kingdom from 2014-2020. Most patients had widespread synchronous metastatic disease. About half had unresected primary tumors, and the majority had received doublet chemotherapy induction, which was irinotecan-based in 57%.
The authors found that patients receiving capecitabine maintenance therapy showed significant improvements in PFS (hazard ratio, 0.40; P < .0001), but also encountered considerably more toxicity than the surveillance group – including grade 2 or higher fatigue (25% vs. 12%), diarrhea (23% vs. 13%), and hand-foot skin reactions (26% vs. 3%).
Perhaps most notably, the treatment group did not experience an overall survival benefit (HR, 0.93; 95% confidence interval, 0.69-1.27; P = .66).
Overall, the authors noted, the main advantage of active maintenance was to delay the return of aggressive chemotherapy combinations for a few months.
With previous trials reporting pretty much the same findings, there is now “overwhelming level-one evidence” that surveillance is an “appropriate” option with “less time on therapy, lower toxicity, and in a number of studies, better quality of life,” which are all important factors for patients, according to Dr. Adams and colleagues in a follow-up letter.
A viable option
The current study pushes back on existing standards, which support maintenance therapy and can prevent patients from being offered active surveillance.
According to Dr. Adams and colleagues, “FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for [metastatic] CRC.”
In addition, the FOCUS4-N trial suggests that oral capecitabine alone – instead of alongside intravenous bevacizumab (Avastin) every 3 weeks – is probably adequate for mCRC maintenance.
“It has been shown that single-agent bevacizumab is both ineffective and highly uneconomic” in the mCRC maintenance setting, “suggesting that it may be the capecitabine element of the combination that” provides the PFS benefit, the team noted.
An editorial accompanying the study also concluded that “treatment holidays are an equally viable and more cost-effective alternative” to maintenance and one of special interest to patients looking for a break after intensive induction.
“For patients, caregivers, and oncologists alike who are hesitant to ... stop therapy completely, it is important to note that” at least in trials, patients under surveillance “continue to be vigilantly monitored, including imaging every 8-12 weeks and symptom assessment every few weeks,” Pashtoon Murtaza Kasi, MD, medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian, Manhattan, said in his editorial.
Interestingly, Dr. Kasi pointed out, the trial found no difference in quality-of-life scores between the study arms in the FOCUS4-N trial.
The two groups scored similarly on mobility, self-care, usual activities, anxiety, and depression, and patients in the capecitabine group reported slightly less pain and discomfort, which may have occurred because of delayed disease progression.
“Although it is somewhat reassuring that maintenance approaches do not adversely affect overall quality of life and functioning, it does not mean that these regimens are free from side effects,” Dr. Kasi writes, adding that it’s possible the surveys missed the impacts of increased toxicity with maintenance therapy.
Caveats to the study
A letter published in the Journal of Clinical Oncology raises questions about the generalizability of the FOCUS4-N results.
In the letter, Annika Kurreck, MD, and colleagues from Charity-University Medicine Berlin, Germany, highlighted that the trial only included patients without actionable biomarkers, which likely meant the study population had particularly aggressive disease. This possibility is supported by the “dramatically short” PFS reported in FOCUS4-N compared with prior maintenance versus surveillance investigations.
In addition, the letter writers caution that the study was underpowered to detect an overall survival benefit.
“Therefore, it might be hypothesized that FOCUS4-N comprised a cohort of patients with a rather aggressive tumor biology and/or high tumor load, leading to a quick failure of any de-escalation treatment strategy,” Dr. Kurreck and colleagues write.
In a response letter, Dr. Adams and his team countered that there’s no consistent evidence from past trials suggesting that patients with poorer prognostic features are unfit for surveillance. “We believe that it is a common misrepresentation of the evidence that all patients with worse prognostic features need to be maintained on active but toxic combination therapies for longer,” they said.
Instead of a blanket approach, maintenance versus surveillance should be “an assessment guided by the clinician listening to and guiding the patient rather than a molecular or biologically measurable parameter,” they write.
Dr. Adams and colleagues agreed that identifying subgroups of patients who are more likely to benefit from maintenance versus surveillance is required research, which “we plan to undertake.”
The work was funded by Cancer Research UK and the National Institute for Health Research. Many of the investigators had industry ties, including Dr. Adams, who reported various relationships with and payments from Merck, Amgen, and others. Dr. Kasi also had ties to several companies, including Bristol Myers Squibb, Lilly, and AstraZeneca. Dr. Kurreck and the other letter writers had numerous company ties as well, including relationships and payments from Roche, the maker of bevacizumab.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL ONCOLOGY
Women at higher risk of serious adverse events from cancer therapy
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
Increase in late-stage cancer diagnoses after pandemic
at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.
“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.
As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.
The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”
The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.
While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.
The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.
It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.
After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).
Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.
One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.
No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.
A version of this article first appeared on Medscape.com.
at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.
“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.
As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.
The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”
The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.
While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.
The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.
It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.
After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).
Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.
One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.
No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.
A version of this article first appeared on Medscape.com.
at Moores Cancer Center in La Jolla, Calif., according to a research letter in JAMA Network Open.
“The number of patients presenting at late, incurable stages is increasing,” say the authors, led by Jade Zifei Zhou, MD, PhD, a hematology/oncology fellow at the center, which is affiliated with the University of California, San Diego.
As the pandemic unfolded and much of routine medicine was put on hold, the postponement or delay in mammograms, colonoscopies, and other screenings led many cancer experts to warn of trouble ahead. In June 2020, for instance, the National Cancer Institute predicted tens of thousands of excess cancer deaths through 2030 because of missed screenings and delays in care.
The message now, Dr. Zhou and colleagues say, is that “patients who have delayed preventative care during the pandemic should be encouraged to resume treatment as soon as possible.”
The team compared the number of people presenting to their cancer center with stage I and IV disease, either for a new diagnosis or a second opinion, during 2019 and with the number during 2020, the first year of the pandemic. The review included over 500 patients, almost 90% of whom were women aged 58 years on average.
While 63.9% of patients with breast cancer presented with stage I disease in 2019, 51.3% did so in 2020. Conversely, while just 1.9% presented with stage IV breast cancer in 2019, the number went up to 6.2% in 2020.
The numbers were even worse from January through March 2021, with only 41.9% of women presenting with stage I and 8% presenting with stage IV breast cancer.
It was the same story for colon cancer, but because of smaller numbers, the findings were not statistically significant.
After the start of the pandemic, the number of patients presenting with stage I colon cancer fell from 17.8% (eight patients) to 14.6% (six patients), while stage IV presentations climbed from 6.7% (three) to 19.5% (eight).
Across all cancer types, stage I presentations fell from 31.9% in 2019 to 29% in 2020, while stage IV presentations rose from 26% to 26.4%.
One of the study limitations is that the patients who came in for a second opinion could have been newly diagnosed but might also have been referred for refractory disease, the authors comment.
No funding for this study was reported. Senior author Kathryn Ann Gold, MD, reported personal fees from AstraZeneca, Takeda, Rakuten, and Regeneron as well as grants from Pfizer and Pharmacyclics.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
New PET tracer detects more metastases in cancer patients
leading to predictions of a “paradigm shift” in this field.
The new tracer, 68Ga-FAPI (fibroblast activation protein inhibitor), detected more metastases in patients with lung cancer than the standard tracer, 18F-FDG (fluorodeoxyglucose), which has been in use for years.
The study by Chinese researchers was published in Radiology.
The team imaged 34 lung cancer patients with both 68Ga-FAPI and 18F-FDG. Performance was similar for primary tumors and for lung, liver, and adrenal gland metastases. However, FAPI imaging detected more metastases in the lymph nodes (356 vs. 320), brain (23 vs. 10), bone (109 vs. 91), and pleura (66 vs. 35). However, neither modality outperformed MRI for brain metastases, the researchers note.
An accompanying editorial concluded that 68Ga-FAPI PET/CT scanning marks “an important paradigm shift to more specific identification and characterization of a variety of cancers.”
“This may also mark the arrival of a new era in nuclear medicine where molecular imaging helps visualize and characterize the entire tumor burden in one setting,” write editorialists Francine Jacobson, MD, and Annick Van den Abbeele, MD, from Harvard University and Brigham and Women’s Hospital and the Dana Farber Cancer Center, in Boston.
This study was the one of the latest in a fast-growing body of literature reporting that tracers targeting FAP with a small-molecule inhibitor (FAPI) outperform FDG tracers, not just in lung cancer but across a broad range of cancers, including breast, hepatic, gastrointestinal, head-neck, gynecologic, and many other tumor types.
The possibilities aren’t limited to imaging, either. Several companies are planning trials to target FAP with radiopharmaceuticals.
FAP is associated with wound repair and is highly expressed by the fibroblasts tightly packed in with cancer cells, particularly in stroma-dense tumors. FAP is rarely expressed by healthy tissue.
The underlying idea is to deliver a radionuclide to cancer-associated fibroblasts, using either a positron emitter, such as gallium-68 (68Ga), for PET imaging or a beta particle or other short-radiation emitter to kill nearby cancer cells as part of treatment.
Targeting FAP holds the promise of PET imaging that is more selective for cancer than FDG. FDG resolution depends on glucose uptake, which is high in active tumors but is also high in inflamed tissues as well as in the brain, gastrointestinal tract, and other areas. Uptake by background tissue can make it difficult to distinguish tumors from their surroundings. FDG uptake can also be lower in small and indolent tumors.
On the therapy side, there’s hope that FAP targeting will lead to radiopharmaceuticals that work across tumor types, not just in specific cancers.
High interest in FAP
Overall, FAP “is a target of high interest for the whole medical oncology community. The preliminary data are good, but this will take a while” to get to market, said Jeremie Calais, MD, a nuclear medicine specialist and FAP researcher at the University of California, Los Angeles.
Interest in FAP as a radiopharmaceutical target is being driven by the success of two agents that have served as a kind of proof of concept, Dr. Calais said.
The first is Novartis’s 177Lu-PSMA-617, which was granted priority review by the U.S. Food and Drug Administration in September 2021 following phase 3 results that showed a progression-free survival benefit of about 5 months when added to standard of care for metastatic castration-resistant prostate cancer, as well as an overall survival benefit of 4 months.
PSMA-617 binds prostate cancer cells that express prostate-specific membrane antigen. The lutetium-177 (177Lu) bombards them with beta particles and gamma radiation.
FAP researchers are also encouraged by the success of 177Lu dotatate (Lutathera), from Advanced Accelerator Applications, which delivers the radionucleotide to gastroenteropancreatic neuroendocrine tumors that express somatostatin receptors.
The FDA approved this agent in 2018 in part on the basis of phase 3 results that found a 20-month progression-free survival of 65.2% when Lutathera was added to octreotide for metastatic disease vs. 10.8% when it wasn’t.
Novartis is now looking into developing FAP-targeted radiopharmaceuticals, along with Clovis and Point Biopharma, among others.
“That’s the key goal” of industry research, “more so than FAP as a diagnostic tool,” Dr. Calais commented to this news organization. There’s “huge potential” if it works out, he said, in part because it won’t be limited to one tumor type.
Clovis recently launched a phase 1/2 trial of its candidate, 177Lu-FAP-2286, for advanced/metastatic solid tumors.
In the company’s “luMIERE” trial, subjects will be infused with 68Ga-FAP-2286 to image the tumor. Once uptake is confirmed, they’ll be infused with 177Lu-FAP-2286 for treatment.
The two-step process – uptake confirmation, then treatment – is dubbed “theranostics” and is the standard approach for radiopharmaceutical therapy, Dr. Calais said.
His own team is working to confirm that imaging accurately reflects FAP expression in tumors by comparing preoperative imaging results with FAP expression on surgical specimens. So far, his team has found that they are strongly correlated.
FAPI PET imaging research is much farther along than therapeutic applications, with almost 200 research articles listed on PubMed in 2021, up from just 3 in 2018. One 2019 paper reported “remarkably high uptake and image contrast” across 28 cancers in 80 patients, including breast, esophagus, lung, pancreatic, head-neck, and colorectal tumors.
Imaging studies so far have tended to be small, with many currently focused on identifying the optimal molecule for targeting FAP and the best positron emitter to combine with it.
FAPI tracers are not available yet commercially, so researchers are creating them themselves. One team recently reported it’s recipe for automated synthesis using commercially available synthesis modules.
Sofie, a maker of FDG and other tracers, hopes to change that and is working to bring FAP tracers to market. The company announced in November 2021 a phase 2 study of 68Ga FAPI-46 to image pancreatic ductal adenocarcinoma. It’s the first step in a broader development program for oncologic and nononcologic indications, Sofie said in a press release.
Dr. Calais sees potential for indications where FAPI has already outperformed FDG in the literature, particularly for gastrointestinal cancers. He doesn’t think it will ever replace FDG for indications such as lymphoma, where it “works perfectly well.”
“On the other hand, you have lesions located in a tissue that has some background level” of FDG uptake. “These things are okay with FDG, but I think maybe FAP can help” because of the improved signal-to-noise ratio, Dr. Calais commented. Unlike FDG, “you mostly never see background uptake with FAP-imaging agents,” he said.
Other pluses include quicker distribution throughout the body than FDG, so scan times are shorter, and also patients do not need to fast beforehand.
Dr. Calais predicts that FAPI tracers will reach the market within 5 years.
A version of this article first appeared on Medscape.com.
leading to predictions of a “paradigm shift” in this field.
The new tracer, 68Ga-FAPI (fibroblast activation protein inhibitor), detected more metastases in patients with lung cancer than the standard tracer, 18F-FDG (fluorodeoxyglucose), which has been in use for years.
The study by Chinese researchers was published in Radiology.
The team imaged 34 lung cancer patients with both 68Ga-FAPI and 18F-FDG. Performance was similar for primary tumors and for lung, liver, and adrenal gland metastases. However, FAPI imaging detected more metastases in the lymph nodes (356 vs. 320), brain (23 vs. 10), bone (109 vs. 91), and pleura (66 vs. 35). However, neither modality outperformed MRI for brain metastases, the researchers note.
An accompanying editorial concluded that 68Ga-FAPI PET/CT scanning marks “an important paradigm shift to more specific identification and characterization of a variety of cancers.”
“This may also mark the arrival of a new era in nuclear medicine where molecular imaging helps visualize and characterize the entire tumor burden in one setting,” write editorialists Francine Jacobson, MD, and Annick Van den Abbeele, MD, from Harvard University and Brigham and Women’s Hospital and the Dana Farber Cancer Center, in Boston.
This study was the one of the latest in a fast-growing body of literature reporting that tracers targeting FAP with a small-molecule inhibitor (FAPI) outperform FDG tracers, not just in lung cancer but across a broad range of cancers, including breast, hepatic, gastrointestinal, head-neck, gynecologic, and many other tumor types.
The possibilities aren’t limited to imaging, either. Several companies are planning trials to target FAP with radiopharmaceuticals.
FAP is associated with wound repair and is highly expressed by the fibroblasts tightly packed in with cancer cells, particularly in stroma-dense tumors. FAP is rarely expressed by healthy tissue.
The underlying idea is to deliver a radionuclide to cancer-associated fibroblasts, using either a positron emitter, such as gallium-68 (68Ga), for PET imaging or a beta particle or other short-radiation emitter to kill nearby cancer cells as part of treatment.
Targeting FAP holds the promise of PET imaging that is more selective for cancer than FDG. FDG resolution depends on glucose uptake, which is high in active tumors but is also high in inflamed tissues as well as in the brain, gastrointestinal tract, and other areas. Uptake by background tissue can make it difficult to distinguish tumors from their surroundings. FDG uptake can also be lower in small and indolent tumors.
On the therapy side, there’s hope that FAP targeting will lead to radiopharmaceuticals that work across tumor types, not just in specific cancers.
High interest in FAP
Overall, FAP “is a target of high interest for the whole medical oncology community. The preliminary data are good, but this will take a while” to get to market, said Jeremie Calais, MD, a nuclear medicine specialist and FAP researcher at the University of California, Los Angeles.
Interest in FAP as a radiopharmaceutical target is being driven by the success of two agents that have served as a kind of proof of concept, Dr. Calais said.
The first is Novartis’s 177Lu-PSMA-617, which was granted priority review by the U.S. Food and Drug Administration in September 2021 following phase 3 results that showed a progression-free survival benefit of about 5 months when added to standard of care for metastatic castration-resistant prostate cancer, as well as an overall survival benefit of 4 months.
PSMA-617 binds prostate cancer cells that express prostate-specific membrane antigen. The lutetium-177 (177Lu) bombards them with beta particles and gamma radiation.
FAP researchers are also encouraged by the success of 177Lu dotatate (Lutathera), from Advanced Accelerator Applications, which delivers the radionucleotide to gastroenteropancreatic neuroendocrine tumors that express somatostatin receptors.
The FDA approved this agent in 2018 in part on the basis of phase 3 results that found a 20-month progression-free survival of 65.2% when Lutathera was added to octreotide for metastatic disease vs. 10.8% when it wasn’t.
Novartis is now looking into developing FAP-targeted radiopharmaceuticals, along with Clovis and Point Biopharma, among others.
“That’s the key goal” of industry research, “more so than FAP as a diagnostic tool,” Dr. Calais commented to this news organization. There’s “huge potential” if it works out, he said, in part because it won’t be limited to one tumor type.
Clovis recently launched a phase 1/2 trial of its candidate, 177Lu-FAP-2286, for advanced/metastatic solid tumors.
In the company’s “luMIERE” trial, subjects will be infused with 68Ga-FAP-2286 to image the tumor. Once uptake is confirmed, they’ll be infused with 177Lu-FAP-2286 for treatment.
The two-step process – uptake confirmation, then treatment – is dubbed “theranostics” and is the standard approach for radiopharmaceutical therapy, Dr. Calais said.
His own team is working to confirm that imaging accurately reflects FAP expression in tumors by comparing preoperative imaging results with FAP expression on surgical specimens. So far, his team has found that they are strongly correlated.
FAPI PET imaging research is much farther along than therapeutic applications, with almost 200 research articles listed on PubMed in 2021, up from just 3 in 2018. One 2019 paper reported “remarkably high uptake and image contrast” across 28 cancers in 80 patients, including breast, esophagus, lung, pancreatic, head-neck, and colorectal tumors.
Imaging studies so far have tended to be small, with many currently focused on identifying the optimal molecule for targeting FAP and the best positron emitter to combine with it.
FAPI tracers are not available yet commercially, so researchers are creating them themselves. One team recently reported it’s recipe for automated synthesis using commercially available synthesis modules.
Sofie, a maker of FDG and other tracers, hopes to change that and is working to bring FAP tracers to market. The company announced in November 2021 a phase 2 study of 68Ga FAPI-46 to image pancreatic ductal adenocarcinoma. It’s the first step in a broader development program for oncologic and nononcologic indications, Sofie said in a press release.
Dr. Calais sees potential for indications where FAPI has already outperformed FDG in the literature, particularly for gastrointestinal cancers. He doesn’t think it will ever replace FDG for indications such as lymphoma, where it “works perfectly well.”
“On the other hand, you have lesions located in a tissue that has some background level” of FDG uptake. “These things are okay with FDG, but I think maybe FAP can help” because of the improved signal-to-noise ratio, Dr. Calais commented. Unlike FDG, “you mostly never see background uptake with FAP-imaging agents,” he said.
Other pluses include quicker distribution throughout the body than FDG, so scan times are shorter, and also patients do not need to fast beforehand.
Dr. Calais predicts that FAPI tracers will reach the market within 5 years.
A version of this article first appeared on Medscape.com.
leading to predictions of a “paradigm shift” in this field.
The new tracer, 68Ga-FAPI (fibroblast activation protein inhibitor), detected more metastases in patients with lung cancer than the standard tracer, 18F-FDG (fluorodeoxyglucose), which has been in use for years.
The study by Chinese researchers was published in Radiology.
The team imaged 34 lung cancer patients with both 68Ga-FAPI and 18F-FDG. Performance was similar for primary tumors and for lung, liver, and adrenal gland metastases. However, FAPI imaging detected more metastases in the lymph nodes (356 vs. 320), brain (23 vs. 10), bone (109 vs. 91), and pleura (66 vs. 35). However, neither modality outperformed MRI for brain metastases, the researchers note.
An accompanying editorial concluded that 68Ga-FAPI PET/CT scanning marks “an important paradigm shift to more specific identification and characterization of a variety of cancers.”
“This may also mark the arrival of a new era in nuclear medicine where molecular imaging helps visualize and characterize the entire tumor burden in one setting,” write editorialists Francine Jacobson, MD, and Annick Van den Abbeele, MD, from Harvard University and Brigham and Women’s Hospital and the Dana Farber Cancer Center, in Boston.
This study was the one of the latest in a fast-growing body of literature reporting that tracers targeting FAP with a small-molecule inhibitor (FAPI) outperform FDG tracers, not just in lung cancer but across a broad range of cancers, including breast, hepatic, gastrointestinal, head-neck, gynecologic, and many other tumor types.
The possibilities aren’t limited to imaging, either. Several companies are planning trials to target FAP with radiopharmaceuticals.
FAP is associated with wound repair and is highly expressed by the fibroblasts tightly packed in with cancer cells, particularly in stroma-dense tumors. FAP is rarely expressed by healthy tissue.
The underlying idea is to deliver a radionuclide to cancer-associated fibroblasts, using either a positron emitter, such as gallium-68 (68Ga), for PET imaging or a beta particle or other short-radiation emitter to kill nearby cancer cells as part of treatment.
Targeting FAP holds the promise of PET imaging that is more selective for cancer than FDG. FDG resolution depends on glucose uptake, which is high in active tumors but is also high in inflamed tissues as well as in the brain, gastrointestinal tract, and other areas. Uptake by background tissue can make it difficult to distinguish tumors from their surroundings. FDG uptake can also be lower in small and indolent tumors.
On the therapy side, there’s hope that FAP targeting will lead to radiopharmaceuticals that work across tumor types, not just in specific cancers.
High interest in FAP
Overall, FAP “is a target of high interest for the whole medical oncology community. The preliminary data are good, but this will take a while” to get to market, said Jeremie Calais, MD, a nuclear medicine specialist and FAP researcher at the University of California, Los Angeles.
Interest in FAP as a radiopharmaceutical target is being driven by the success of two agents that have served as a kind of proof of concept, Dr. Calais said.
The first is Novartis’s 177Lu-PSMA-617, which was granted priority review by the U.S. Food and Drug Administration in September 2021 following phase 3 results that showed a progression-free survival benefit of about 5 months when added to standard of care for metastatic castration-resistant prostate cancer, as well as an overall survival benefit of 4 months.
PSMA-617 binds prostate cancer cells that express prostate-specific membrane antigen. The lutetium-177 (177Lu) bombards them with beta particles and gamma radiation.
FAP researchers are also encouraged by the success of 177Lu dotatate (Lutathera), from Advanced Accelerator Applications, which delivers the radionucleotide to gastroenteropancreatic neuroendocrine tumors that express somatostatin receptors.
The FDA approved this agent in 2018 in part on the basis of phase 3 results that found a 20-month progression-free survival of 65.2% when Lutathera was added to octreotide for metastatic disease vs. 10.8% when it wasn’t.
Novartis is now looking into developing FAP-targeted radiopharmaceuticals, along with Clovis and Point Biopharma, among others.
“That’s the key goal” of industry research, “more so than FAP as a diagnostic tool,” Dr. Calais commented to this news organization. There’s “huge potential” if it works out, he said, in part because it won’t be limited to one tumor type.
Clovis recently launched a phase 1/2 trial of its candidate, 177Lu-FAP-2286, for advanced/metastatic solid tumors.
In the company’s “luMIERE” trial, subjects will be infused with 68Ga-FAP-2286 to image the tumor. Once uptake is confirmed, they’ll be infused with 177Lu-FAP-2286 for treatment.
The two-step process – uptake confirmation, then treatment – is dubbed “theranostics” and is the standard approach for radiopharmaceutical therapy, Dr. Calais said.
His own team is working to confirm that imaging accurately reflects FAP expression in tumors by comparing preoperative imaging results with FAP expression on surgical specimens. So far, his team has found that they are strongly correlated.
FAPI PET imaging research is much farther along than therapeutic applications, with almost 200 research articles listed on PubMed in 2021, up from just 3 in 2018. One 2019 paper reported “remarkably high uptake and image contrast” across 28 cancers in 80 patients, including breast, esophagus, lung, pancreatic, head-neck, and colorectal tumors.
Imaging studies so far have tended to be small, with many currently focused on identifying the optimal molecule for targeting FAP and the best positron emitter to combine with it.
FAPI tracers are not available yet commercially, so researchers are creating them themselves. One team recently reported it’s recipe for automated synthesis using commercially available synthesis modules.
Sofie, a maker of FDG and other tracers, hopes to change that and is working to bring FAP tracers to market. The company announced in November 2021 a phase 2 study of 68Ga FAPI-46 to image pancreatic ductal adenocarcinoma. It’s the first step in a broader development program for oncologic and nononcologic indications, Sofie said in a press release.
Dr. Calais sees potential for indications where FAPI has already outperformed FDG in the literature, particularly for gastrointestinal cancers. He doesn’t think it will ever replace FDG for indications such as lymphoma, where it “works perfectly well.”
“On the other hand, you have lesions located in a tissue that has some background level” of FDG uptake. “These things are okay with FDG, but I think maybe FAP can help” because of the improved signal-to-noise ratio, Dr. Calais commented. Unlike FDG, “you mostly never see background uptake with FAP-imaging agents,” he said.
Other pluses include quicker distribution throughout the body than FDG, so scan times are shorter, and also patients do not need to fast beforehand.
Dr. Calais predicts that FAPI tracers will reach the market within 5 years.
A version of this article first appeared on Medscape.com.
FROM RADIOLOGY
EMA panel endorses two cancer drugs, one sickle cell drug
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.