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Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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