AVAHO

This transcript has been edited for clarity.

As anyone who has been through medical training will tell you, some little scenes just stick with you. I had been seeing a patient in our resident clinic in West Philly for a couple of years. She was in her mid-60s with diabetes and hypertension and a distant smoking history. She was overweight and had been trying to improve her diet and lose weight since I started seeing her. One day she came in and was delighted to report that she had finally started shedding some pounds — about 15 in the past 2 months.

I enthusiastically told my preceptor that my careful dietary counseling had finally done the job. She looked through the chart for a moment and asked, “Is she up to date on her cancer screening?” A workup revealed adenocarcinoma of the lung. The patient did well, actually, but the story stuck with me.

The textbooks call it “unintentional weight loss,” often in big, scary letters, and every doctor will go just a bit pale if a patient tells them that, despite efforts not to, they are losing weight. But true unintentional weight loss is not that common. After all, most of us are at least half-heartedly trying to lose weight all the time. Should doctors be worried when we are successful?

A new study suggests that perhaps they should. We’re talking about this study, appearing in JAMA, which combined participants from two long-running observational cohorts: 120,000 women from the Nurses’ Health Study, and 50,000 men from the Health Professionals Follow-Up Study. (These cohorts started in the 1970s and 1980s, so we’ll give them a pass on the gender-specific study designs.)

The rationale of enrolling healthcare providers in these cohort studies is that they would be reliable witnesses of their own health status. If a nurse or doctor says they have pancreatic cancer, it’s likely that they truly have pancreatic cancer. Detailed health surveys were distributed to the participants every other year, and the average follow-up was more than a decade.

JAMA

JAMA

JAMA

JAMA

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

As anyone who has been through medical training will tell you, some little scenes just stick with you. I had been seeing a patient in our resident clinic in West Philly for a couple of years. She was in her mid-60s with diabetes and hypertension and a distant smoking history. She was overweight and had been trying to improve her diet and lose weight since I started seeing her. One day she came in and was delighted to report that she had finally started shedding some pounds — about 15 in the past 2 months.

I enthusiastically told my preceptor that my careful dietary counseling had finally done the job. She looked through the chart for a moment and asked, “Is she up to date on her cancer screening?” A workup revealed adenocarcinoma of the lung. The patient did well, actually, but the story stuck with me.

The textbooks call it “unintentional weight loss,” often in big, scary letters, and every doctor will go just a bit pale if a patient tells them that, despite efforts not to, they are losing weight. But true unintentional weight loss is not that common. After all, most of us are at least half-heartedly trying to lose weight all the time. Should doctors be worried when we are successful?

A new study suggests that perhaps they should. We’re talking about this study, appearing in JAMA, which combined participants from two long-running observational cohorts: 120,000 women from the Nurses’ Health Study, and 50,000 men from the Health Professionals Follow-Up Study. (These cohorts started in the 1970s and 1980s, so we’ll give them a pass on the gender-specific study designs.)

The rationale of enrolling healthcare providers in these cohort studies is that they would be reliable witnesses of their own health status. If a nurse or doctor says they have pancreatic cancer, it’s likely that they truly have pancreatic cancer. Detailed health surveys were distributed to the participants every other year, and the average follow-up was more than a decade.

JAMA

JAMA

JAMA

JAMA

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

As anyone who has been through medical training will tell you, some little scenes just stick with you. I had been seeing a patient in our resident clinic in West Philly for a couple of years. She was in her mid-60s with diabetes and hypertension and a distant smoking history. She was overweight and had been trying to improve her diet and lose weight since I started seeing her. One day she came in and was delighted to report that she had finally started shedding some pounds — about 15 in the past 2 months.

I enthusiastically told my preceptor that my careful dietary counseling had finally done the job. She looked through the chart for a moment and asked, “Is she up to date on her cancer screening?” A workup revealed adenocarcinoma of the lung. The patient did well, actually, but the story stuck with me.

The textbooks call it “unintentional weight loss,” often in big, scary letters, and every doctor will go just a bit pale if a patient tells them that, despite efforts not to, they are losing weight. But true unintentional weight loss is not that common. After all, most of us are at least half-heartedly trying to lose weight all the time. Should doctors be worried when we are successful?

A new study suggests that perhaps they should. We’re talking about this study, appearing in JAMA, which combined participants from two long-running observational cohorts: 120,000 women from the Nurses’ Health Study, and 50,000 men from the Health Professionals Follow-Up Study. (These cohorts started in the 1970s and 1980s, so we’ll give them a pass on the gender-specific study designs.)

The rationale of enrolling healthcare providers in these cohort studies is that they would be reliable witnesses of their own health status. If a nurse or doctor says they have pancreatic cancer, it’s likely that they truly have pancreatic cancer. Detailed health surveys were distributed to the participants every other year, and the average follow-up was more than a decade.

JAMA

JAMA

JAMA

JAMA

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

When the American Cancer Society recently unveiled changes to its lung cancer screening guidance, the aim was to remove barriers to screening and catch more cancers in high-risk people earlier.

Although the lung cancer death rate has declined significantly over the past few decades, lung cancer remains the leading cause of cancer deaths worldwide.

Detecting lung cancer early is key to improving survival. Still, lung cancer screening rates are poor. In 2021, the American Lung Association estimated that 14 million US adults qualified for lung cancer screening, but only 5.8% received it.

Smokers or former smokers without symptoms may forgo regular screening and only receive their screening scan after symptoms emerge, explained Janani S. Reisenauer, MD, Division Chair of Thoracic Surgery at Mayo Clinic, Rochester, Minnesota. But by the time symptoms develop, the cancer is typically more advanced, and treatment options become more limited.

The goal of the new American Cancer Society guidelines, published in early November 2023 in CA: A Cancer Journal for Physicians, is to identify lung cancers at earlier stages when they are easier to treat.

The new guidelines, which update a 2013 version, expand the eligibility age for screening and the pool of current and former smokers who qualify for annual screening with low-dose CT. Almost 5 million more high-risk people will now qualify for regular lung cancer screening, the guideline authors estimated.

But will expanding screening help reduce deaths from lung cancer? And perhaps just as important, will the guidelines move the needle on the “disappointingly low” lung cancer screening rates up to this point?

“I definitely think it’s a step in the right direction,” said Lecia V. Sequist, MD, MPH, clinical researcher and lung cancer medical oncologist, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.

As people age, their risk for lung cancer increases, so it makes sense to screen all former smokers regardless of when they quit, explained Kim Lori Sandler, MD, from Vanderbilt University Medical Center, Nashville, Tennessee, and cochair of the American College of Radiology’s Lung Cancer Screening Steering Committee.

“There’s really nothing magical or drastic that happens at the 15-year mark,” Dr. Sequist agreed. For “someone who quit 14 years ago versus 16 years ago, it is essentially the same risk, and so scientifically it doesn’t really make sense to impose an artificial cut-off where no change in risk exists.”

The latest evidence reviewed in the new guidelines shows that expanding the guidelines would identify more early-stage cancers and potentially save lives. The authors modeled the benefits and harms of lung cancer screening using several scenarios.

Moving the start age from 55 to 50 years would lead to a 15% reduction in lung cancer mortality in men aged 50-54 years, the model suggested.

Removing the 15-year timeline for quitting smoking also would also improve outcomes. Compared with scenarios that included the 15-year quit timeline for former smokers, those that removed the limit would result in a 37.3% increase in screening exams, a 21% increase in would avert lung cancer deaths, and offer a 19% increase in life-years gained per 100,000 population.

Overall, the evidence indicates that, “if fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States,” the guideline authors wrote.

But screening more people also comes with risks, such as more false-positive findings, which could lead to extra scans, invasive tests for tissue sampling, or even procedures for benign disease, Dr. Sandler explained. The latter “is what we really need to avoid.”

Even so, Dr. Sandler believes the current guidelines show that the benefit of screening “is great enough that it’s worth including these additional individuals.”
 

Guidelines Are Not Enough

But will expanding the screening criteria prompt more eligible individuals to receive their CT scans?

Simply expanding the eligibility criteria, by itself, likely won’t measurably improve screening uptake, said Paolo Boffetta, MD, MPH, of Stony Brook Cancer Center, Stony Brook, New York.

Healthcare and insurance access along with patient demand may present the most significant barriers to improving screening uptake.

The “issue is not the guideline as much as it’s the healthcare system,” said Otis W. Brawley, MD, professor of oncology at the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Access to screening at hospitals with limited CT scanners and staff could present one major issue.

When Dr. Brawley worked at a large inner-city safety net hospital in Atlanta, patients with lung cancer frequently had to wait over a week to use one of the four CT scanners, he recalled. Adding to these delays, we didn’t have enough people to read the screens or enough people to do the diagnostics for those who had abnormalities, said Dr. Brawley.

To increase lung cancer screening in this context would increase the wait time for patients who do have cancer, he said.

Insurance coverage could present a roadblock for some as well. While the 2021 US Preventive Services Task Force (USPSTF) recommendations largely align with the new ones from the American Cancer Society, there’s one key difference: The USPSTF still requires former smokers to have quit within 15 years to be eligible for annual screening.

Because the USPSTF recommendations dictate insurance coverage, some former smokers — those who quit more than 15 years ago — may not qualify for coverage and would have to pay out-of-pocket for screening.

Dr. Sequist, however, had a more optimistic outlook about screening uptake.

The American Cancer Society guidelines should remove some of the stigma surrounding lung cancer screening. Most people, when asked a lot of questions about their tobacco use and history, tend to downplay it because there’s shame associated with smoking, Dr. Sequist said. The new guidelines limit the information needed to determine eligibility.

Dr. Sequist also noted that the updated American Cancer Society guideline would improve screening rates because it simplifies the eligibility criteria and makes it easier for physicians to determine who qualifies.

The issue, however, is that some of these individuals — those who quit over 15 years ago — may not have their scan covered by insurance, which could preclude lower-income individuals from getting screened.

The American Cancer Society guidelines” do not necessarily translate into a change in policy,” which is “dictated by the USPSTF and payors such as Medicare,” explained Peter Mazzone, MD, MPH, director of the Lung Cancer Program and Lung Cancer Screening Program for the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

On the patient side, Dr. Brawley noted, “we don’t yet have a large demand” for screening.

Many current and former smokers may put off lung cancer screening or not seek it out. Some may be unaware of their eligibility, while others may fear the outcome of a scan. Even among eligible individuals who do receive an initial scan, most — more than 75% — do not return for their next scan a year later, research showed.

Enhancing patient education and launching strong marketing campaigns would be a key element to encourage more people to get their annual screening and reduce the stigma associated with lung cancer as a smoker’s disease.

“Primary care physicians are integral in ensuring all eligible patients receive appropriate screening for lung cancer,” said Steven P. Furr, MD, president of the American Academy of Family Physicians and a family physician in Jackson, Alabama. “It is imperative that family physicians encourage screening in at-risk patients and counsel them on the importance of continued screening, as well as smoking cessation, if needed.”

Two authors of the new guidelines reported financial relationships with Seno Medical Instruments, the Genentech Foundation, Crispr Therapeutics, BEAM Therapeutics, Intellia Therapeutics, Editas Medicine, Freenome, and Guardant Health.

A version of this article appeared on Medscape.com.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

Overall cancer mortality in the United States has continued to decline, with more than 4 million cancer deaths averted since 1991, according to the 2024 American Cancer Society (ACS) annual report on cancer trends.

The “good news is that we are continuing to see a decline in cancer mortality,” which follows the steady decline we’ve observed in cancer mortality over the past three decades, Rebecca Siegel, MPH, with ACS, and lead author of the new report, told this news organization.

However, these gains are “threatened by increasing incidence for many common cancers, including 6 of the top 10 most commonly diagnosed cancers,” Ms. Siegel said.

Overall, new cancer diagnoses are projected to top 2 million in 2024. That’s an average of 5480 new diagnoses each day or one person diagnosed every 15 seconds.

“In the US, the way our healthcare system is designed, we like to treat more than we like to prevent disease, and I would personally like to see a shift towards more emphasis on cancer prevention,” she added.

The full report was published in CA: A Cancer Journal for Clinicians.

Cancer Hitting at Younger Ages

Although advancing age remains the strongest determinate of cancer risk, the new data showed that cancer incidence is steadily increasing in younger populations.

What’s most alarming is the increase in cancer diagnoses in adults under 50 years.

Between 2015 and 2019, incidence rates increased by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers, by 1%-2% annually for cervical cancer in women between 30 and 44 years, and by 2%-3% annually for prostate, kidney, melanoma, and human papillomavirus (HPV)–associated oral cancers, as well as liver cancer in women.

The continuing rise in colorectal cancer (CRC) incidence in younger adults, in particular, is “very concerning,” Ms. Siegel said, and has shifted mortality patterns among adults younger than 50 years.

In this group, CRC is now the leading cause of cancer death in men and the second-leading cause in women behind breast cancer — up from the fourth leading cause of cancer death in both younger men and women 2 decades ago.

The obesity epidemic is likely a contributing factor in rising CRC rates, “but it’s not the whole story,” Ms. Siegel told this news organization. “A lot of work is going on to try to uncover what exactly is causing an increased risk of colorectal cancer.”

The proportion of new cancers diagnosed in adults aged 50-64 years has also increased — from 25% in 1995 to 30% in 2019-2020 — while the proportion of new cancers diagnosed in adults aged 65 years and older fell from 61% to 58% in that time frame. Among this older population, the authors observed steep declines in the incidence of prostate cancer and smoking-related cancers.

“Every generation born after the 1950s has had higher cancer risk than the previous generation. That tells us is that there is some exposure that is yet unknown that is causing this increased risk,” Ms. Siegel noted.

To halt and reverse this trend, it will be important to increase screening uptake as well as awareness of noninvasive stool tests and follow-up care in younger adults, Ahmedin Jemal, PhD, with ACS, commented in a press release.

Other key findings in the report include the sharp decline in cervical cancer incidence rates in women in their 20s — the first cohort to receive the HPV vaccine — but increases of nearly 2% in women 30-44 years, highlighting the need for more screening in young women as well as broader uptake of the vaccine, the authors said.

After decades of increases, cancer incidence in children has leveled off, although rates continue to increase among adolescents aged 15-19 years. The largest increase was a 4% per year rise in thyroid cancer, much of which is likely due to overdiagnosis.

On the survival front, uterine cancer is the only cancer for which survival decreased over the past few decades.

Progress against cancer has been hampered by persistent and widespread cancer disparities. Mortality rates are twofold higher among Black patients with prostate, stomach, and endometrial cancers than among White patients, and twofold higher among Native Americans with liver, stomach, and kidney cancers.

Black women are more often diagnosed at more advanced stages (44% vs 23%) and have worse 5‐year survival rates (63% vs 84%) than White women.

“This report underscores the need for public policy interventions to help reduce these cancer disparities and save more lives,” Lisa Lacasse, with the ACS Cancer Action Network, said in the release. “We urge lawmakers at all levels of government to advance policies that ensure more people have health insurance coverage as well as improved access to and affordability of care, such as increased funding for cancer research and screening programs.”

The authors of a linked editorial noted that while the report shows continued progress in oncology overall, certain ethnic, racial, age, and geographic populations face a disproportionate burden of cancer incidence and mortality.

“Like others, we find these health disparities wholly unacceptable and agree with the National Cancer Plan and Biden Moonshot Initiative that bold and new collaborations and thinking will be needed to produce different outcomes,” the editorialists said.

Overall, the editorialists noted, “every 15 seconds presents a real reminder of the urgency to end cancer as we know it for everyone.”

A version of this article appeared on Medscape.com.

Overall cancer mortality in the United States has continued to decline, with more than 4 million cancer deaths averted since 1991, according to the 2024 American Cancer Society (ACS) annual report on cancer trends.

The “good news is that we are continuing to see a decline in cancer mortality,” which follows the steady decline we’ve observed in cancer mortality over the past three decades, Rebecca Siegel, MPH, with ACS, and lead author of the new report, told this news organization.

However, these gains are “threatened by increasing incidence for many common cancers, including 6 of the top 10 most commonly diagnosed cancers,” Ms. Siegel said.

Overall, new cancer diagnoses are projected to top 2 million in 2024. That’s an average of 5480 new diagnoses each day or one person diagnosed every 15 seconds.

“In the US, the way our healthcare system is designed, we like to treat more than we like to prevent disease, and I would personally like to see a shift towards more emphasis on cancer prevention,” she added.

The full report was published in CA: A Cancer Journal for Clinicians.

Cancer Hitting at Younger Ages

Although advancing age remains the strongest determinate of cancer risk, the new data showed that cancer incidence is steadily increasing in younger populations.

What’s most alarming is the increase in cancer diagnoses in adults under 50 years.

Between 2015 and 2019, incidence rates increased by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers, by 1%-2% annually for cervical cancer in women between 30 and 44 years, and by 2%-3% annually for prostate, kidney, melanoma, and human papillomavirus (HPV)–associated oral cancers, as well as liver cancer in women.

The continuing rise in colorectal cancer (CRC) incidence in younger adults, in particular, is “very concerning,” Ms. Siegel said, and has shifted mortality patterns among adults younger than 50 years.

In this group, CRC is now the leading cause of cancer death in men and the second-leading cause in women behind breast cancer — up from the fourth leading cause of cancer death in both younger men and women 2 decades ago.

The obesity epidemic is likely a contributing factor in rising CRC rates, “but it’s not the whole story,” Ms. Siegel told this news organization. “A lot of work is going on to try to uncover what exactly is causing an increased risk of colorectal cancer.”

The proportion of new cancers diagnosed in adults aged 50-64 years has also increased — from 25% in 1995 to 30% in 2019-2020 — while the proportion of new cancers diagnosed in adults aged 65 years and older fell from 61% to 58% in that time frame. Among this older population, the authors observed steep declines in the incidence of prostate cancer and smoking-related cancers.

“Every generation born after the 1950s has had higher cancer risk than the previous generation. That tells us is that there is some exposure that is yet unknown that is causing this increased risk,” Ms. Siegel noted.

To halt and reverse this trend, it will be important to increase screening uptake as well as awareness of noninvasive stool tests and follow-up care in younger adults, Ahmedin Jemal, PhD, with ACS, commented in a press release.

Other key findings in the report include the sharp decline in cervical cancer incidence rates in women in their 20s — the first cohort to receive the HPV vaccine — but increases of nearly 2% in women 30-44 years, highlighting the need for more screening in young women as well as broader uptake of the vaccine, the authors said.

After decades of increases, cancer incidence in children has leveled off, although rates continue to increase among adolescents aged 15-19 years. The largest increase was a 4% per year rise in thyroid cancer, much of which is likely due to overdiagnosis.

On the survival front, uterine cancer is the only cancer for which survival decreased over the past few decades.

Progress against cancer has been hampered by persistent and widespread cancer disparities. Mortality rates are twofold higher among Black patients with prostate, stomach, and endometrial cancers than among White patients, and twofold higher among Native Americans with liver, stomach, and kidney cancers.

Black women are more often diagnosed at more advanced stages (44% vs 23%) and have worse 5‐year survival rates (63% vs 84%) than White women.

“This report underscores the need for public policy interventions to help reduce these cancer disparities and save more lives,” Lisa Lacasse, with the ACS Cancer Action Network, said in the release. “We urge lawmakers at all levels of government to advance policies that ensure more people have health insurance coverage as well as improved access to and affordability of care, such as increased funding for cancer research and screening programs.”

The authors of a linked editorial noted that while the report shows continued progress in oncology overall, certain ethnic, racial, age, and geographic populations face a disproportionate burden of cancer incidence and mortality.

“Like others, we find these health disparities wholly unacceptable and agree with the National Cancer Plan and Biden Moonshot Initiative that bold and new collaborations and thinking will be needed to produce different outcomes,” the editorialists said.

Overall, the editorialists noted, “every 15 seconds presents a real reminder of the urgency to end cancer as we know it for everyone.”

A version of this article appeared on Medscape.com.

Overall cancer mortality in the United States has continued to decline, with more than 4 million cancer deaths averted since 1991, according to the 2024 American Cancer Society (ACS) annual report on cancer trends.

The “good news is that we are continuing to see a decline in cancer mortality,” which follows the steady decline we’ve observed in cancer mortality over the past three decades, Rebecca Siegel, MPH, with ACS, and lead author of the new report, told this news organization.

However, these gains are “threatened by increasing incidence for many common cancers, including 6 of the top 10 most commonly diagnosed cancers,” Ms. Siegel said.

Overall, new cancer diagnoses are projected to top 2 million in 2024. That’s an average of 5480 new diagnoses each day or one person diagnosed every 15 seconds.

“In the US, the way our healthcare system is designed, we like to treat more than we like to prevent disease, and I would personally like to see a shift towards more emphasis on cancer prevention,” she added.

The full report was published in CA: A Cancer Journal for Clinicians.

Cancer Hitting at Younger Ages

Although advancing age remains the strongest determinate of cancer risk, the new data showed that cancer incidence is steadily increasing in younger populations.

What’s most alarming is the increase in cancer diagnoses in adults under 50 years.

Between 2015 and 2019, incidence rates increased by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers, by 1%-2% annually for cervical cancer in women between 30 and 44 years, and by 2%-3% annually for prostate, kidney, melanoma, and human papillomavirus (HPV)–associated oral cancers, as well as liver cancer in women.

The continuing rise in colorectal cancer (CRC) incidence in younger adults, in particular, is “very concerning,” Ms. Siegel said, and has shifted mortality patterns among adults younger than 50 years.

In this group, CRC is now the leading cause of cancer death in men and the second-leading cause in women behind breast cancer — up from the fourth leading cause of cancer death in both younger men and women 2 decades ago.

The obesity epidemic is likely a contributing factor in rising CRC rates, “but it’s not the whole story,” Ms. Siegel told this news organization. “A lot of work is going on to try to uncover what exactly is causing an increased risk of colorectal cancer.”

The proportion of new cancers diagnosed in adults aged 50-64 years has also increased — from 25% in 1995 to 30% in 2019-2020 — while the proportion of new cancers diagnosed in adults aged 65 years and older fell from 61% to 58% in that time frame. Among this older population, the authors observed steep declines in the incidence of prostate cancer and smoking-related cancers.

“Every generation born after the 1950s has had higher cancer risk than the previous generation. That tells us is that there is some exposure that is yet unknown that is causing this increased risk,” Ms. Siegel noted.

To halt and reverse this trend, it will be important to increase screening uptake as well as awareness of noninvasive stool tests and follow-up care in younger adults, Ahmedin Jemal, PhD, with ACS, commented in a press release.

Other key findings in the report include the sharp decline in cervical cancer incidence rates in women in their 20s — the first cohort to receive the HPV vaccine — but increases of nearly 2% in women 30-44 years, highlighting the need for more screening in young women as well as broader uptake of the vaccine, the authors said.

After decades of increases, cancer incidence in children has leveled off, although rates continue to increase among adolescents aged 15-19 years. The largest increase was a 4% per year rise in thyroid cancer, much of which is likely due to overdiagnosis.

On the survival front, uterine cancer is the only cancer for which survival decreased over the past few decades.

Progress against cancer has been hampered by persistent and widespread cancer disparities. Mortality rates are twofold higher among Black patients with prostate, stomach, and endometrial cancers than among White patients, and twofold higher among Native Americans with liver, stomach, and kidney cancers.

Black women are more often diagnosed at more advanced stages (44% vs 23%) and have worse 5‐year survival rates (63% vs 84%) than White women.

“This report underscores the need for public policy interventions to help reduce these cancer disparities and save more lives,” Lisa Lacasse, with the ACS Cancer Action Network, said in the release. “We urge lawmakers at all levels of government to advance policies that ensure more people have health insurance coverage as well as improved access to and affordability of care, such as increased funding for cancer research and screening programs.”

The authors of a linked editorial noted that while the report shows continued progress in oncology overall, certain ethnic, racial, age, and geographic populations face a disproportionate burden of cancer incidence and mortality.

“Like others, we find these health disparities wholly unacceptable and agree with the National Cancer Plan and Biden Moonshot Initiative that bold and new collaborations and thinking will be needed to produce different outcomes,” the editorialists said.

Overall, the editorialists noted, “every 15 seconds presents a real reminder of the urgency to end cancer as we know it for everyone.”

A version of this article appeared on Medscape.com.

TOPLINE:

New data provide no support for an increased risk for pancreatic cancer with use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for up to 7 years, although longer-term data are needed, researchers said.

METHODOLOGY:

• Some studies have raised concern about a possible increased risk for pancreatitis and pancreatic cancer in patients taking a GLP-1 RA. 
• Investigators behind this population-based cohort study assessed the association of GLP-1 RA treatment with pancreatic cancer incidence over a median of 7 years in 543,595 adults (mean age, 59.9 years; 51% women) with type 2 diabetes. 
• Treatment with basal insulin was used as an active comparator. 
• The analyses accounted for major confounding factors and time-related biases and adjusted for treatment with other glucose-lowering medications and a history of pancreatitis. 

TAKEAWAY: 

• During the study period, 33,377 patients (6.1%) used GLP-1 RAs and 106,849 (19.7%) used basal insulin, with 1665 of all patients diagnosed with pancreatic cancer. 
• There was no evidence that GLP-1 RA use increased pancreatic cancer risk compared with basal insulin. 
• The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of one defined daily dose per day of GLP-1 RA compared with basal insulin in years 5-7 was 0.50 (95% CI, 0.15-1.71). 
• New-user and prevalent new-user analyses showed HRs from year 5 onward following initiation of a GLP-1 RA vs basal insulin was 0.52 (95% CI, 0.19-1.41) and 0.75 (95% CI, 0.37-1.53), respectively. 

IN PRACTICE: 

Using several analytical approaches, these findings do not suggest an increase in pancreatic cancer incidence over 7 years following the start of GLP-1 RA treatment, according to the investigation. “However, monitoring for pancreatic cancer risk beyond 7 years following initiation of treatment is still required,” the authors wrote.

SOURCE:

The study, with first author Rachel Dankner, MD, MPH, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Israel, was published online on January 4, 2024, in JAMA Network Open. 

LIMITATIONS: 

Data on the exact type of GLP-1 RA were not available. The analyses accounted for history of pancreatitis but not alcohol use or exposure to pesticides/chemicals. Because of the risk for bias due to reverse causation, an emphasis was placed on drug effects several years after their initiation. However, this reduced the number of pancreatic cancer cases available and led to estimated HRs with wider CIs. 

DISCLOSURES: 

The study received no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data provide no support for an increased risk for pancreatic cancer with use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for up to 7 years, although longer-term data are needed, researchers said.

METHODOLOGY:

• Some studies have raised concern about a possible increased risk for pancreatitis and pancreatic cancer in patients taking a GLP-1 RA. 
• Investigators behind this population-based cohort study assessed the association of GLP-1 RA treatment with pancreatic cancer incidence over a median of 7 years in 543,595 adults (mean age, 59.9 years; 51% women) with type 2 diabetes. 
• Treatment with basal insulin was used as an active comparator. 
• The analyses accounted for major confounding factors and time-related biases and adjusted for treatment with other glucose-lowering medications and a history of pancreatitis. 

TAKEAWAY: 

• During the study period, 33,377 patients (6.1%) used GLP-1 RAs and 106,849 (19.7%) used basal insulin, with 1665 of all patients diagnosed with pancreatic cancer. 
• There was no evidence that GLP-1 RA use increased pancreatic cancer risk compared with basal insulin. 
• The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of one defined daily dose per day of GLP-1 RA compared with basal insulin in years 5-7 was 0.50 (95% CI, 0.15-1.71). 
• New-user and prevalent new-user analyses showed HRs from year 5 onward following initiation of a GLP-1 RA vs basal insulin was 0.52 (95% CI, 0.19-1.41) and 0.75 (95% CI, 0.37-1.53), respectively. 

IN PRACTICE: 

Using several analytical approaches, these findings do not suggest an increase in pancreatic cancer incidence over 7 years following the start of GLP-1 RA treatment, according to the investigation. “However, monitoring for pancreatic cancer risk beyond 7 years following initiation of treatment is still required,” the authors wrote.

SOURCE:

The study, with first author Rachel Dankner, MD, MPH, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Israel, was published online on January 4, 2024, in JAMA Network Open. 

LIMITATIONS: 

Data on the exact type of GLP-1 RA were not available. The analyses accounted for history of pancreatitis but not alcohol use or exposure to pesticides/chemicals. Because of the risk for bias due to reverse causation, an emphasis was placed on drug effects several years after their initiation. However, this reduced the number of pancreatic cancer cases available and led to estimated HRs with wider CIs. 

DISCLOSURES: 

The study received no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data provide no support for an increased risk for pancreatic cancer with use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for up to 7 years, although longer-term data are needed, researchers said.

METHODOLOGY:

• Some studies have raised concern about a possible increased risk for pancreatitis and pancreatic cancer in patients taking a GLP-1 RA. 
• Investigators behind this population-based cohort study assessed the association of GLP-1 RA treatment with pancreatic cancer incidence over a median of 7 years in 543,595 adults (mean age, 59.9 years; 51% women) with type 2 diabetes. 
• Treatment with basal insulin was used as an active comparator. 
• The analyses accounted for major confounding factors and time-related biases and adjusted for treatment with other glucose-lowering medications and a history of pancreatitis. 

TAKEAWAY: 

• During the study period, 33,377 patients (6.1%) used GLP-1 RAs and 106,849 (19.7%) used basal insulin, with 1665 of all patients diagnosed with pancreatic cancer. 
• There was no evidence that GLP-1 RA use increased pancreatic cancer risk compared with basal insulin. 
• The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of one defined daily dose per day of GLP-1 RA compared with basal insulin in years 5-7 was 0.50 (95% CI, 0.15-1.71). 
• New-user and prevalent new-user analyses showed HRs from year 5 onward following initiation of a GLP-1 RA vs basal insulin was 0.52 (95% CI, 0.19-1.41) and 0.75 (95% CI, 0.37-1.53), respectively. 

IN PRACTICE: 

Using several analytical approaches, these findings do not suggest an increase in pancreatic cancer incidence over 7 years following the start of GLP-1 RA treatment, according to the investigation. “However, monitoring for pancreatic cancer risk beyond 7 years following initiation of treatment is still required,” the authors wrote.

SOURCE:

The study, with first author Rachel Dankner, MD, MPH, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Israel, was published online on January 4, 2024, in JAMA Network Open. 

LIMITATIONS: 

Data on the exact type of GLP-1 RA were not available. The analyses accounted for history of pancreatitis but not alcohol use or exposure to pesticides/chemicals. Because of the risk for bias due to reverse causation, an emphasis was placed on drug effects several years after their initiation. However, this reduced the number of pancreatic cancer cases available and led to estimated HRs with wider CIs. 

DISCLOSURES: 

The study received no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Lung cancer is the deadliest cancer in the world, largely because so many patients are diagnosed late.

Screening more patients could help, yet screening rates remain critically low. In the United States, only about 6% of eligible people get screened , according to the American Lung Association. Contrast that with screening rates for breast, cervical, and colorectal cancer, which all top 70%.

But what if lung cancer detection was as simple as taking a puff on an inhaler and following up with a urine test?

Researchers at the Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, have developed nanosensors that target lung cancer proteins and can be delivered via inhaler or nebulizer, according to research published this month in Science Advances. If the sensors spot these proteins, they produce a signal in the urine that can be detected with a paper test strip.

“It’s a more complex version of a pregnancy test, but it’s very simple to use,” said Qian Zhong, PhD, an MIT researcher and co-lead author of the study.

Currently, the only recommended screening test for lung cancer is low-dose CT. But not everyone has easy access to screening facilities, said the other co-lead author Edward Tan, PhD, a former MIT postdoc and currently a scientist at the biotech company Prime Medicine, Cambridge, Massachusetts.

“Our focus is to provide an alternative for the early detection of lung cancer that does not rely on resource-intensive infrastructure,” said Dr. Tan. “Most developing countries don’t have such resources” — and residents in some parts of the United States don’t have easy access, either, he said.
 

How It Works

The sensors are polymer nanoparticles coated in DNA barcodes, short DNA sequences that are unique and easy to identify. The researchers engineered the particles to be targeted by protease enzymes linked to stage I lung adenocarcinoma. Upon contact, the proteases cleave off the barcodes, which make their way into the bloodstream and are excreted in urine. A test strip can detect them, revealing results about 20 minutes from the time it’s dipped.

The researchers tested this system in mice genetically engineered to develop human-like lung tumors. Using aerosol nebulizers, they delivered 20 sensors to mice with the equivalent of stage I or II cancer. Using a machine learning algorithm, they identified the four most accurate sensors. With 100% specificity, those four sensors exhibited sensitivity of 84.6%.

“One advantage of using inhalation is that it’s noninvasive, and another advantage is that it distributes across the lung quite homogeneously,” said Dr. Tan. The time from inhalation to detection is also relatively fast — in mice, the whole process took about 2 hours, and Dr. Zhong speculated that it would not be much longer in humans.
 

Other Applications and Challenges

An injectable version of this technology, also developed at MIT, has already been tested in a phase 1 clinical trial for diagnosing liver cancer and nonalcoholic steatohepatitis. The injection also works in tandem with a urine test, the researchers showed in 2021. According to Tan, his research group (led by  Sangeeta Bhatia, MD, PhD) was the first to describe this type of technology to screen for diseases.

The lab is also working toward using inhalable sensors to distinguish between viral, bacterial, and fungal pneumonia. And the technology could also be used to diagnose other lung conditions like asthma and chronic obstructive pulmonary disease, Dr. Tan said.

The tech is certainly “innovative,” remarked Gaetano Rocco, MD, a thoracic surgeon and lung cancer researcher at Memorial Sloan Kettering Cancer Center, Basking Ridge, New Jersey, who was not involved in the study.

Still, challenges may arise when applying it to people. Many factors are involved in regulating fluid volume, potentially interfering with the ability to detect the compounds in the urine, Rocco said. Diet, hydration, drug interference, renal function, and some chronic diseases could all limit effectiveness.

Another challenge: Human cancer can be more heterogeneous (containing different kinds of cancer cells), so four sensors may not be enough, Zhong said. He and colleagues are beginning to analyze human biopsy samples to see whether the same sensors that worked in mice would also work in humans. If all goes well, they hope to do studies on humans or nonhuman primates.
 

A version of this article appeared on Medscape.com.

Lung cancer is the deadliest cancer in the world, largely because so many patients are diagnosed late.

Screening more patients could help, yet screening rates remain critically low. In the United States, only about 6% of eligible people get screened , according to the American Lung Association. Contrast that with screening rates for breast, cervical, and colorectal cancer, which all top 70%.

But what if lung cancer detection was as simple as taking a puff on an inhaler and following up with a urine test?

Researchers at the Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, have developed nanosensors that target lung cancer proteins and can be delivered via inhaler or nebulizer, according to research published this month in Science Advances. If the sensors spot these proteins, they produce a signal in the urine that can be detected with a paper test strip.

“It’s a more complex version of a pregnancy test, but it’s very simple to use,” said Qian Zhong, PhD, an MIT researcher and co-lead author of the study.

Currently, the only recommended screening test for lung cancer is low-dose CT. But not everyone has easy access to screening facilities, said the other co-lead author Edward Tan, PhD, a former MIT postdoc and currently a scientist at the biotech company Prime Medicine, Cambridge, Massachusetts.

“Our focus is to provide an alternative for the early detection of lung cancer that does not rely on resource-intensive infrastructure,” said Dr. Tan. “Most developing countries don’t have such resources” — and residents in some parts of the United States don’t have easy access, either, he said.
 

How It Works

The sensors are polymer nanoparticles coated in DNA barcodes, short DNA sequences that are unique and easy to identify. The researchers engineered the particles to be targeted by protease enzymes linked to stage I lung adenocarcinoma. Upon contact, the proteases cleave off the barcodes, which make their way into the bloodstream and are excreted in urine. A test strip can detect them, revealing results about 20 minutes from the time it’s dipped.

The researchers tested this system in mice genetically engineered to develop human-like lung tumors. Using aerosol nebulizers, they delivered 20 sensors to mice with the equivalent of stage I or II cancer. Using a machine learning algorithm, they identified the four most accurate sensors. With 100% specificity, those four sensors exhibited sensitivity of 84.6%.

“One advantage of using inhalation is that it’s noninvasive, and another advantage is that it distributes across the lung quite homogeneously,” said Dr. Tan. The time from inhalation to detection is also relatively fast — in mice, the whole process took about 2 hours, and Dr. Zhong speculated that it would not be much longer in humans.
 

Other Applications and Challenges

An injectable version of this technology, also developed at MIT, has already been tested in a phase 1 clinical trial for diagnosing liver cancer and nonalcoholic steatohepatitis. The injection also works in tandem with a urine test, the researchers showed in 2021. According to Tan, his research group (led by  Sangeeta Bhatia, MD, PhD) was the first to describe this type of technology to screen for diseases.

The lab is also working toward using inhalable sensors to distinguish between viral, bacterial, and fungal pneumonia. And the technology could also be used to diagnose other lung conditions like asthma and chronic obstructive pulmonary disease, Dr. Tan said.

The tech is certainly “innovative,” remarked Gaetano Rocco, MD, a thoracic surgeon and lung cancer researcher at Memorial Sloan Kettering Cancer Center, Basking Ridge, New Jersey, who was not involved in the study.

Still, challenges may arise when applying it to people. Many factors are involved in regulating fluid volume, potentially interfering with the ability to detect the compounds in the urine, Rocco said. Diet, hydration, drug interference, renal function, and some chronic diseases could all limit effectiveness.

Another challenge: Human cancer can be more heterogeneous (containing different kinds of cancer cells), so four sensors may not be enough, Zhong said. He and colleagues are beginning to analyze human biopsy samples to see whether the same sensors that worked in mice would also work in humans. If all goes well, they hope to do studies on humans or nonhuman primates.
 

A version of this article appeared on Medscape.com.

Lung cancer is the deadliest cancer in the world, largely because so many patients are diagnosed late.

Screening more patients could help, yet screening rates remain critically low. In the United States, only about 6% of eligible people get screened , according to the American Lung Association. Contrast that with screening rates for breast, cervical, and colorectal cancer, which all top 70%.

But what if lung cancer detection was as simple as taking a puff on an inhaler and following up with a urine test?

Researchers at the Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, have developed nanosensors that target lung cancer proteins and can be delivered via inhaler or nebulizer, according to research published this month in Science Advances. If the sensors spot these proteins, they produce a signal in the urine that can be detected with a paper test strip.

“It’s a more complex version of a pregnancy test, but it’s very simple to use,” said Qian Zhong, PhD, an MIT researcher and co-lead author of the study.

Currently, the only recommended screening test for lung cancer is low-dose CT. But not everyone has easy access to screening facilities, said the other co-lead author Edward Tan, PhD, a former MIT postdoc and currently a scientist at the biotech company Prime Medicine, Cambridge, Massachusetts.

“Our focus is to provide an alternative for the early detection of lung cancer that does not rely on resource-intensive infrastructure,” said Dr. Tan. “Most developing countries don’t have such resources” — and residents in some parts of the United States don’t have easy access, either, he said.
 

How It Works

The sensors are polymer nanoparticles coated in DNA barcodes, short DNA sequences that are unique and easy to identify. The researchers engineered the particles to be targeted by protease enzymes linked to stage I lung adenocarcinoma. Upon contact, the proteases cleave off the barcodes, which make their way into the bloodstream and are excreted in urine. A test strip can detect them, revealing results about 20 minutes from the time it’s dipped.

The researchers tested this system in mice genetically engineered to develop human-like lung tumors. Using aerosol nebulizers, they delivered 20 sensors to mice with the equivalent of stage I or II cancer. Using a machine learning algorithm, they identified the four most accurate sensors. With 100% specificity, those four sensors exhibited sensitivity of 84.6%.

“One advantage of using inhalation is that it’s noninvasive, and another advantage is that it distributes across the lung quite homogeneously,” said Dr. Tan. The time from inhalation to detection is also relatively fast — in mice, the whole process took about 2 hours, and Dr. Zhong speculated that it would not be much longer in humans.
 

Other Applications and Challenges

An injectable version of this technology, also developed at MIT, has already been tested in a phase 1 clinical trial for diagnosing liver cancer and nonalcoholic steatohepatitis. The injection also works in tandem with a urine test, the researchers showed in 2021. According to Tan, his research group (led by  Sangeeta Bhatia, MD, PhD) was the first to describe this type of technology to screen for diseases.

The lab is also working toward using inhalable sensors to distinguish between viral, bacterial, and fungal pneumonia. And the technology could also be used to diagnose other lung conditions like asthma and chronic obstructive pulmonary disease, Dr. Tan said.

The tech is certainly “innovative,” remarked Gaetano Rocco, MD, a thoracic surgeon and lung cancer researcher at Memorial Sloan Kettering Cancer Center, Basking Ridge, New Jersey, who was not involved in the study.

Still, challenges may arise when applying it to people. Many factors are involved in regulating fluid volume, potentially interfering with the ability to detect the compounds in the urine, Rocco said. Diet, hydration, drug interference, renal function, and some chronic diseases could all limit effectiveness.

Another challenge: Human cancer can be more heterogeneous (containing different kinds of cancer cells), so four sensors may not be enough, Zhong said. He and colleagues are beginning to analyze human biopsy samples to see whether the same sensors that worked in mice would also work in humans. If all goes well, they hope to do studies on humans or nonhuman primates.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.