AVAHO

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

The antibody-drug conjugate trastuzumab deruxtecan, or T-DXd, is an effective first-line treatment in patients with HER2-low metastatic breast cancer, conferring an additional 5 months’ progression-free survival over chemotherapy.

HER2-low cancers express levels of human epidermal growth factor receptor 2 that are below standard thresholds for HER2-positive immunohistochemistry. In 2022, results from the DESTINY-Breast04 trial showed T-DXd (Enhertu, AstraZeneca) to be an effective second-line chemotherapy in patients with HER2-low metastatic breast cancer.

The highly awaited new findings, from the manufacturer-sponsored, open-label Phase 3 DESTINY-Breast06 trial, were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The findings not only definitively establish a role for T-DXd earlier in the treatment sequence for HER2-low cancers, they also suggest benefit in a group of patients designated for the purposes of this trial to be HER2-ultralow. These patients have cancers with only faintly detectable HER2 expression on currently used assays (J Clin Oncol 42, 2024 [suppl 17; abstr LBA 1000]).

In a separate set of findings also presented at ASCO, from the randomized phase 1B open-label study, DESTINY-Breast07, T-Dxd showed efficacy in previously untreated HER2-positive metastatic breast cancer patients both alone and in combination with the monoclonal antibody pertuzumab (Perjeta, Genentech).
 

DESTINY-Breast06 Methods and Results

The DESTINY-Breast06 findings were presented by lead investigator Guiseppe Curigliano, MD, PhD, of the University of Milan and European Institute of Oncology. Dr. Curigliano and his colleagues randomized 866 patients with metastatic breast cancer: 436 to intravenous T-Dxd and 430 to the investigator’s choice of capecitabine, nab-paclitaxel, or paclitaxel chemotherapy. The investigators chose capecitabine 60% of the time.

Most patients had cancers classed as HER2 low (immunohistochemistry 1+ or 2+), while 153 had cancers classed by investigators as HER2-ultralow (IHC 0 with membrane staining or IHC under 1+). Patients enrolled in the study were those whose disease had progressed after endocrine therapy with or without targeted therapy. Patients’ median age was between 57 and 58, and all were chemotherapy-naive in the metastatic breast cancer setting.

The main outcome of the study was median progression-free survival in the HER2-low group. T-Dxd was seen improving progression-free survival, with median 13.2 months vs. 8.1 months (hazard ratio, 0.62; 95% confidence interval, 0.51-0.74; P < .0001). In the intention-to-treat population, which included the HER2 ultralow patients, the benefit was the same (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). This suggested that T-DXd is also effective in these patients, and it will be extremely important going forward to identify the lowest level of HER2 expression in metastatic breast cancers that can still benefit from therapy with T-DxD, Dr. Curigliano said.

Overall survival could not be assessed in the study cohort because complete data were not yet available, Dr. Curigliano said. However, trends pointed to an advantage for T-DXd, and tumor response rates were markedly higher with T-DXd: 57% compared with 31% for standard chemotherapy in the full cohort.

Serious treatment-emergent adverse events were more common in the T-Dxd–treated patients, with 11% of that arm developing drug-related interstitial lung disease, and three patients dying of it. Five patients in the T-DXd arm died of adverse events deemed treatment-related, and none died from treatment-related adverse events in the standard chemotherapy arm. Altogether 11 patients died in the T-DXd arm and 6 in the chemotherapy arm.
 

Clinical Implications of DESTINY-Breast06

The DESTINY-Breast06 data show that “we have to again change how we think about HER2 expression. Even very low levels of HER2 expression matter, and they can be leveraged to improve the treatment for our patients,” said Ian Krop, MD, PhD, of the Yale Cancer Center in New Haven, Connecticut, during the session where the results were presented.

But T-DXd may not be an appropriate first choice for all patients, especially given the safety concerns associated with T-DXd, he continued. With overall survival and quality-of-life data still lacking, clinicians will have to determine on a case-by-case basis who should get T-DXd in the first line.

“For patients who have symptomatic metastatic disease, who need a response to address those symptoms, those in whom you think chemotherapy may not work as well because they had, for example, a short recurrence interval after their adjuvant chemotherapy — using T-DXd in that first-line setting makes perfect sense to take advantage of the substantially higher response rate compared to chemo,” Dr. Krop said. “But for patients who have asymptomatic low burdens of disease, it seems very reasonable to consider using a well-tolerated chemotherapy like capecitabine in the first line, and then using T-DXd in the second line.”

In an interview, Erica Mayer, MD, of the Dana Farber Cancer Institute in Boston, Massachusetts, said patient choice will also matter in determining whether T-DXd is a first-line option. The known toxicity of T-DXd was underscored by the latest findings, she noted, while capecitabine, one of the chemotherapy choices in the control arm of the study, “really reflects what the majority of breast cancer doctors tend to offer, both because of the efficacy of the drug, but also because it’s oral, it’s well tolerated, and you don’t lose your hair.”
 

DESTINY-Breast07 Results

The DESTINY-Breast07 findings, from a Phase 1B open-label trial measuring safety and tolerability, were presented by Fabrice Andre, MD, PhD, of Université Paris Saclay in Paris, France. Dr. Andre and his colleagues presented the first data comparing T-DXd monotherapy and T-DXd with pertuzumab — a monoclonal antibody targeting HER2 — as a first-line treatment in patients with HER2-overexpressing (immunohistochemistry 3 and above) metastatic breast cancer. (J Clin Oncol 42, 2024 [suppl 16; abstr 1009]).

Current first-line standard of care for these patients is pertuzumab, trastuzumab, and docetaxel, based on results from the 2015 CLEOPATRA trial. T-DXd is currently approved as a second-line treatment.

Dr. Andre and his colleagues randomized 75 patients to monotherapy with T-DXd and 50 to combined therapy, with a median follow-up of 2 years.

After 1 year of treatment, combination of T-DXd and pertuzumab was seen to be associated with a progression-free survival of 89% at 1 year (80% CI, 81.9-93.9), compared with 80% in patients treated with T-DXd alone (80% CI, 73.7-86.1). Objective tumor response rate was 84% for the combined therapy at 12 weeks, with 20% of patients seeing a complete response, compared with 76% and 8%, respectively, for monotherapy.

As in the DESTINY-Breast06 trial, adverse events were high, with interstitial lung disease seen in 9% of patients in the monotherapy group and in 14% of the combined-therapy patients, although no treatment-related deaths occurred.

A randomized phase 3 trial, DESTINY Breast09, will now compare the monotherapy and the combined therapy with standard care.

T-DXd has seen a rapidly expanding role in treating breast and other solid tumors. The DESTINY Breast06 findings will move up its place in the treatment algorithm for metastatic breast cancer, “allowing us to now offer T-DXd as the first chemotherapy choice for patients who are making that transition to chemotherapy over many of the traditional provider choices that we previously have offered,” Dr. Mayer said.

The results “support the use of not only this specific agent, but also the concept of antibody drug conjugates as a very effective way to treat malignancy,” she added.

Dr. Curigliano reported receiving speaker’s fees, research funding, and other support from AstraZeneca and Daiichi Sankyo, among other companies, as did most of his co-authors, of whom three were AstraZeneca employees. Dr. Fabrice disclosed receiving research funding, travel compensation, and/or advisory fees from AstraZeneca and other entities, as did several of his co-authors. Two of his co-authors were employed by AstraZeneca and Roche, manufacturers of the study drugs. Dr. Krop and Dr. Mayer disclosed relationships with AstraZeneca and others.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

CHICAGO — Genetics and diet have been among the top theories for what may be fueling the troubling rise of colorectal cancer in young adults. Now, an early look at genetic data from people with colorectal cancer further suggests that the cause is linked to what is happening in the gut.

The findings were presented at the annual meeting of the American Society for Clinical Oncology (ASCO) by researchers from Ohio State University. For the analysis, they analyzed genetic data on tumors.

The researchers found signs that a high-fat, low-fiber diet may increase inflammation in the gut that prevents it from naturally suppressing tumors. The cells of young people with colorectal cancer also appeared to have aged more quickly — by 15 years on average — than a person’s actual age. That’s unusual, because older people with colorectal cancer don’t have the same boost in cellular aging.

The rate of colorectal cancer among young people has been rising at an alarming rate, according to a 2023 report from the American Cancer Society. In 2019, one in five colorectal cancer cases were among people younger than 55. That’s up from 1 in 10 in 1995, which means the rate has doubled in less than 30 years.
 

Need Colon Cancer Screening?

Who needs a colorectal cancer screening? Ask colorectal cancer specialist Nancy Kemeny, MD.

A 2017 analysis estimated that a person’s risk of colorectal cancer increased 12% by eating 3.5 ounces of red or processed meat daily, which is the equivalent of the size of a deck of playing cards. The same study also linked colorectal cancer risk to alcohol intake, citing its ethanol content. Eating a diet high in fiber can reduce a person’s risk.

This latest study aligned with previous findings that link bacteria called Fusobacterium to colorectal cancer. It’s not unusual for Fusobacterium to be present in a person’s mouth, but it is more likely to be found in the intestines of colorectal cancer patients, compared with those of healthy people. One study even found that people with colorectal cancer were five times more likely to have Fusobacterium in their stool, compared with healthy people.

Colorectal cancer is more common among men than women, “likely reflecting differences in risk factor prevalence, such as excess body weight and processed meat consumption,” the authors of the 2023 American Cancer Society report explained.

People younger than 45 should alert their medical provider if they have constipation, rectal bleeding, or sudden changes in bowel movements, which can be symptoms of colorectal cancer. Screening for colorectal cancer should begin for most people at age 45.

A version of this article appeared on WebMD.com.

TOPLINE:

Patients with early-onset colorectal cancer (EOCRC) often present with hematochezia or abdominal pain, symptoms frequently overlooked in younger populations, leading to delays in diagnosis of 4-6 months, a new analysis showed.

METHODOLOGY:

• As the number of cases of EOCRC, defined as colorectal cancer (CRC) diagnosed before age 50, continues to rise, early detection has become increasingly important. Improved recognition of presenting signs and symptoms associated with EOCRC could lead to a more timely diagnosis and better clinical outcomes.
• In a systematic review and meta-analysis of 81 studies with 24.9 million EOCRC cases, researchers sought to determine the most common presenting signs and symptoms, their association with EOCRC risk, and the time from presentation to diagnosis.
• Data extraction and quality assessment were performed independently in duplicate using PRISMA guidelines, and Joanna Briggs Institute critical appraisal tools were used to measure the risk of bias.

TAKEAWAY:

• Hematochezia was the most common presenting sign/symptom, with a pooled prevalence of 45%, followed by abdominal pain, with a pooled prevalence of 40%.
• Altered bowel habits, which included constipation, diarrhea, and alternating bowel habits, were the third most common presenting sign/symptom (pooled prevalence of 27%), followed by unexplained weight loss (pooled prevalence of 17%).
• The likelihood of EOCRC was estimated to be fivefold to 54-fold higher with hematochezia and 1.3-fold to sixfold higher with abdominal pain.
• The mean time from sign or symptom onset to EOCRC diagnosis was 6.4 months (range, 1.8-13.7 months).

IN PRACTICE:

“These findings and the increasing risk of CRC in individuals younger than 50 years highlight the urgent need to educate clinicians and patients about these signs and symptoms to ensure that diagnostic workup and resolution are not delayed. Adapting current clinical practice to identify and address these signs and symptoms through careful clinical triage and follow-up could help limit morbidity and mortality associated with EOCRC,” the authors wrote.

SOURCE:

The study, with Joshua Demb, PhD, MPH, division of gastroenterology, department of medicine, University of California, San Diego, was published online May 24 in JAMA Network Open.

LIMITATIONS:

Significant heterogeneity across studies affected the ability to meta-analyze some results. The cross-sectional data limited the ability to stratify by age, sex, race and ethnicity, or genetic ancestry. It was not possible to evaluate the impact of time to diagnosis on CRC outcomes due to a limited number of studies answering this question. Researchers were unable to examine the constellation of signs and symptoms because they lacked individual-level data from each study.

DISCLOSURES:

The authors disclosed no relevant conflicts of interest. No specific funding was disclosed.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-onset colorectal cancer (EOCRC) often present with hematochezia or abdominal pain, symptoms frequently overlooked in younger populations, leading to delays in diagnosis of 4-6 months, a new analysis showed.

METHODOLOGY:

• As the number of cases of EOCRC, defined as colorectal cancer (CRC) diagnosed before age 50, continues to rise, early detection has become increasingly important. Improved recognition of presenting signs and symptoms associated with EOCRC could lead to a more timely diagnosis and better clinical outcomes.
• In a systematic review and meta-analysis of 81 studies with 24.9 million EOCRC cases, researchers sought to determine the most common presenting signs and symptoms, their association with EOCRC risk, and the time from presentation to diagnosis.
• Data extraction and quality assessment were performed independently in duplicate using PRISMA guidelines, and Joanna Briggs Institute critical appraisal tools were used to measure the risk of bias.

TAKEAWAY:

• Hematochezia was the most common presenting sign/symptom, with a pooled prevalence of 45%, followed by abdominal pain, with a pooled prevalence of 40%.
• Altered bowel habits, which included constipation, diarrhea, and alternating bowel habits, were the third most common presenting sign/symptom (pooled prevalence of 27%), followed by unexplained weight loss (pooled prevalence of 17%).
• The likelihood of EOCRC was estimated to be fivefold to 54-fold higher with hematochezia and 1.3-fold to sixfold higher with abdominal pain.
• The mean time from sign or symptom onset to EOCRC diagnosis was 6.4 months (range, 1.8-13.7 months).

IN PRACTICE:

“These findings and the increasing risk of CRC in individuals younger than 50 years highlight the urgent need to educate clinicians and patients about these signs and symptoms to ensure that diagnostic workup and resolution are not delayed. Adapting current clinical practice to identify and address these signs and symptoms through careful clinical triage and follow-up could help limit morbidity and mortality associated with EOCRC,” the authors wrote.

SOURCE:

The study, with Joshua Demb, PhD, MPH, division of gastroenterology, department of medicine, University of California, San Diego, was published online May 24 in JAMA Network Open.

LIMITATIONS:

Significant heterogeneity across studies affected the ability to meta-analyze some results. The cross-sectional data limited the ability to stratify by age, sex, race and ethnicity, or genetic ancestry. It was not possible to evaluate the impact of time to diagnosis on CRC outcomes due to a limited number of studies answering this question. Researchers were unable to examine the constellation of signs and symptoms because they lacked individual-level data from each study.

DISCLOSURES:

The authors disclosed no relevant conflicts of interest. No specific funding was disclosed.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-onset colorectal cancer (EOCRC) often present with hematochezia or abdominal pain, symptoms frequently overlooked in younger populations, leading to delays in diagnosis of 4-6 months, a new analysis showed.

METHODOLOGY:

• As the number of cases of EOCRC, defined as colorectal cancer (CRC) diagnosed before age 50, continues to rise, early detection has become increasingly important. Improved recognition of presenting signs and symptoms associated with EOCRC could lead to a more timely diagnosis and better clinical outcomes.
• In a systematic review and meta-analysis of 81 studies with 24.9 million EOCRC cases, researchers sought to determine the most common presenting signs and symptoms, their association with EOCRC risk, and the time from presentation to diagnosis.
• Data extraction and quality assessment were performed independently in duplicate using PRISMA guidelines, and Joanna Briggs Institute critical appraisal tools were used to measure the risk of bias.

TAKEAWAY:

• Hematochezia was the most common presenting sign/symptom, with a pooled prevalence of 45%, followed by abdominal pain, with a pooled prevalence of 40%.
• Altered bowel habits, which included constipation, diarrhea, and alternating bowel habits, were the third most common presenting sign/symptom (pooled prevalence of 27%), followed by unexplained weight loss (pooled prevalence of 17%).
• The likelihood of EOCRC was estimated to be fivefold to 54-fold higher with hematochezia and 1.3-fold to sixfold higher with abdominal pain.
• The mean time from sign or symptom onset to EOCRC diagnosis was 6.4 months (range, 1.8-13.7 months).

IN PRACTICE:

“These findings and the increasing risk of CRC in individuals younger than 50 years highlight the urgent need to educate clinicians and patients about these signs and symptoms to ensure that diagnostic workup and resolution are not delayed. Adapting current clinical practice to identify and address these signs and symptoms through careful clinical triage and follow-up could help limit morbidity and mortality associated with EOCRC,” the authors wrote.

SOURCE:

The study, with Joshua Demb, PhD, MPH, division of gastroenterology, department of medicine, University of California, San Diego, was published online May 24 in JAMA Network Open.

LIMITATIONS:

Significant heterogeneity across studies affected the ability to meta-analyze some results. The cross-sectional data limited the ability to stratify by age, sex, race and ethnicity, or genetic ancestry. It was not possible to evaluate the impact of time to diagnosis on CRC outcomes due to a limited number of studies answering this question. Researchers were unable to examine the constellation of signs and symptoms because they lacked individual-level data from each study.

DISCLOSURES:

The authors disclosed no relevant conflicts of interest. No specific funding was disclosed.
 

A version of this article appeared on Medscape.com.

Adding durvalumab as consolidation treatment following concurrent chemoradiation (cCRT) adds 2 years of life and increases progression-free survival by 24%, compared with placebo, in patients with limited stage small cell lung cancer (LS-SCLC).

These are results of the ADRIATIC trial, the first planned interim analysis of the randomized, phase 3, double-blind, placebo-controlled multicenter study comparing the PD-L 1 antibody durvalumab vs placebo in patients with stage I-III limited stage disease and prior concurrent chemoradiotherapy.

Lead author David R. Spigel, MD, drew several rounds of applause from an enthusiastic audience when he presented this data, at the plenary session of the annual meeting of the American Society for Clinical Oncology (ASCO) in Chicago.

“ADRIATIC is the first positive, global phase 3 trial of immunotherapy in limited stage SCLC,” said Lauren Byers, MD, the discussant in the session.

“This groundbreaking trial sets a new standard of care with consolidative durvalumab following concurrent chemoradiation,” continued Dr. Byers, who is professor and thoracic section chief in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Andersen Cancer Center in Houston, Texas.
 

ADRIATIC Methods and Results

The new study enrolled 730 patients and randomized them between 1 and 42 days after concurrent chemoradiation to one of three treatments: durvalumab 1500 mg; durvalumab plus tremelimumab 75 mg; or placebo. Treatment was continued for a maximum of 24 months, or until progression or intolerable toxicity.

The study had dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for durvalumab vs placebo. The researchers have not yet looked at the results for the secondary endpoints of OS and PFS for patients treated with durvalumab plus tremelimumab vs placebo.

After a median follow-up of 3 years, there was a median OS of 55.9 months in the durvalumab-treated patients, compared with 33.4 months in the placebo arm (hazard ratio [HR], 0.73), and, at a median follow-up of 2 years, there was median PFS of 16.6 months vs 9.2 months respectively (HR, 0.76).
 

New Standard of Care for Patients with LS-SCLC

“This study had a very good safety profile,” said Dr. Spigel, who is also a medical oncologist and the chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, during his presentation.

“Looking at severe grade 3 or 4 events, these were nearly identical in either arm at 24%. Looking at any-grade immune-mediated AEs, these were 31.2% and 10.2% respectively, and then looking at radiation pneumonitis or pneumonitis, the rates were 38.2% in the durvalumab arm, compared with 30.2% in the placebo arm,” Dr. Spigel said.

Noting that there have been no major advances in the treatment of LS-SCLC for several decades, with most patients experiencing recurrences within 2 years of the cCRT standard of care, Dr. Spigel said “consolidation durvalumab will become the new standard of care for patients with LS-SCLC who have not progressed after cCRT.”

Toby Campbell, MD, a thoracic oncologist, who is professor and chief of Palliative Care at the University of Wisconsin, in Madison, Wisconsin, agrees.

“I take care of patients with small cell lung cancer, an aggressive cancer with high symptom burden that devastates patients and families in its wake,” said Dr. Campbell, during an interview. “About 15% of patients luckily present when the cancer is still contained in the chest and is potentially curable. However, with current treatments we give, which include chemotherapy together with radiation, we are ‘successful’ at curing one in four people.

“This study presents a new treatment option which makes a big difference to patients like mine,” Dr. Campbell continued. “For example, at the 2-year time point, nearly half of patients are still cancer-free. These folks have the opportunity to live their lives more fully, unburdened by the symptoms and dread this disease brings. If approved, I think this treatment would immediately be appropriate to use in clinic.

“Further, oncologists are comfortable using this medication as it is already FDA-approved and used similarly in non–small cell lung cancer.”

The study was funded by AstraZeneca. Dr. Spigel discloses consulting or advisory roles with Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Ipsen, Jazz Pharmaceuticals, Lyell Immunopharma, MedImmune, Monte Rosa Therapeutics, Novartis, Novocure, and Sanofi/Aventis. He has also received research funding from many companies, and travel, accommodations, and other expense reimbursements from AstraZeneca, Genentech, and Novartis.

Dr. Byers discloses honoraria from and consulting or advisory roles with Abbvie, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Beigene, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Genentech, Jazz Pharmaceuticals, Merck, Dohme, Novartis, and Puma Biotechnology. He also has received research funding from Amgen, AstraZeneca, and Jazz Pharmaceuticals.

Dr. Campbell has served as an advisor for Novocure and Genentech.

Adding durvalumab as consolidation treatment following concurrent chemoradiation (cCRT) adds 2 years of life and increases progression-free survival by 24%, compared with placebo, in patients with limited stage small cell lung cancer (LS-SCLC).

These are results of the ADRIATIC trial, the first planned interim analysis of the randomized, phase 3, double-blind, placebo-controlled multicenter study comparing the PD-L 1 antibody durvalumab vs placebo in patients with stage I-III limited stage disease and prior concurrent chemoradiotherapy.

Lead author David R. Spigel, MD, drew several rounds of applause from an enthusiastic audience when he presented this data, at the plenary session of the annual meeting of the American Society for Clinical Oncology (ASCO) in Chicago.

“ADRIATIC is the first positive, global phase 3 trial of immunotherapy in limited stage SCLC,” said Lauren Byers, MD, the discussant in the session.

“This groundbreaking trial sets a new standard of care with consolidative durvalumab following concurrent chemoradiation,” continued Dr. Byers, who is professor and thoracic section chief in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Andersen Cancer Center in Houston, Texas.
 

ADRIATIC Methods and Results

The new study enrolled 730 patients and randomized them between 1 and 42 days after concurrent chemoradiation to one of three treatments: durvalumab 1500 mg; durvalumab plus tremelimumab 75 mg; or placebo. Treatment was continued for a maximum of 24 months, or until progression or intolerable toxicity.

The study had dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for durvalumab vs placebo. The researchers have not yet looked at the results for the secondary endpoints of OS and PFS for patients treated with durvalumab plus tremelimumab vs placebo.

After a median follow-up of 3 years, there was a median OS of 55.9 months in the durvalumab-treated patients, compared with 33.4 months in the placebo arm (hazard ratio [HR], 0.73), and, at a median follow-up of 2 years, there was median PFS of 16.6 months vs 9.2 months respectively (HR, 0.76).
 

New Standard of Care for Patients with LS-SCLC

“This study had a very good safety profile,” said Dr. Spigel, who is also a medical oncologist and the chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, during his presentation.

“Looking at severe grade 3 or 4 events, these were nearly identical in either arm at 24%. Looking at any-grade immune-mediated AEs, these were 31.2% and 10.2% respectively, and then looking at radiation pneumonitis or pneumonitis, the rates were 38.2% in the durvalumab arm, compared with 30.2% in the placebo arm,” Dr. Spigel said.

Noting that there have been no major advances in the treatment of LS-SCLC for several decades, with most patients experiencing recurrences within 2 years of the cCRT standard of care, Dr. Spigel said “consolidation durvalumab will become the new standard of care for patients with LS-SCLC who have not progressed after cCRT.”

Toby Campbell, MD, a thoracic oncologist, who is professor and chief of Palliative Care at the University of Wisconsin, in Madison, Wisconsin, agrees.

“I take care of patients with small cell lung cancer, an aggressive cancer with high symptom burden that devastates patients and families in its wake,” said Dr. Campbell, during an interview. “About 15% of patients luckily present when the cancer is still contained in the chest and is potentially curable. However, with current treatments we give, which include chemotherapy together with radiation, we are ‘successful’ at curing one in four people.

“This study presents a new treatment option which makes a big difference to patients like mine,” Dr. Campbell continued. “For example, at the 2-year time point, nearly half of patients are still cancer-free. These folks have the opportunity to live their lives more fully, unburdened by the symptoms and dread this disease brings. If approved, I think this treatment would immediately be appropriate to use in clinic.

“Further, oncologists are comfortable using this medication as it is already FDA-approved and used similarly in non–small cell lung cancer.”

The study was funded by AstraZeneca. Dr. Spigel discloses consulting or advisory roles with Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Ipsen, Jazz Pharmaceuticals, Lyell Immunopharma, MedImmune, Monte Rosa Therapeutics, Novartis, Novocure, and Sanofi/Aventis. He has also received research funding from many companies, and travel, accommodations, and other expense reimbursements from AstraZeneca, Genentech, and Novartis.

Dr. Byers discloses honoraria from and consulting or advisory roles with Abbvie, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Beigene, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Genentech, Jazz Pharmaceuticals, Merck, Dohme, Novartis, and Puma Biotechnology. He also has received research funding from Amgen, AstraZeneca, and Jazz Pharmaceuticals.

Dr. Campbell has served as an advisor for Novocure and Genentech.

Adding durvalumab as consolidation treatment following concurrent chemoradiation (cCRT) adds 2 years of life and increases progression-free survival by 24%, compared with placebo, in patients with limited stage small cell lung cancer (LS-SCLC).

These are results of the ADRIATIC trial, the first planned interim analysis of the randomized, phase 3, double-blind, placebo-controlled multicenter study comparing the PD-L 1 antibody durvalumab vs placebo in patients with stage I-III limited stage disease and prior concurrent chemoradiotherapy.

Lead author David R. Spigel, MD, drew several rounds of applause from an enthusiastic audience when he presented this data, at the plenary session of the annual meeting of the American Society for Clinical Oncology (ASCO) in Chicago.

“ADRIATIC is the first positive, global phase 3 trial of immunotherapy in limited stage SCLC,” said Lauren Byers, MD, the discussant in the session.

“This groundbreaking trial sets a new standard of care with consolidative durvalumab following concurrent chemoradiation,” continued Dr. Byers, who is professor and thoracic section chief in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Andersen Cancer Center in Houston, Texas.
 

ADRIATIC Methods and Results

The new study enrolled 730 patients and randomized them between 1 and 42 days after concurrent chemoradiation to one of three treatments: durvalumab 1500 mg; durvalumab plus tremelimumab 75 mg; or placebo. Treatment was continued for a maximum of 24 months, or until progression or intolerable toxicity.

The study had dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for durvalumab vs placebo. The researchers have not yet looked at the results for the secondary endpoints of OS and PFS for patients treated with durvalumab plus tremelimumab vs placebo.

After a median follow-up of 3 years, there was a median OS of 55.9 months in the durvalumab-treated patients, compared with 33.4 months in the placebo arm (hazard ratio [HR], 0.73), and, at a median follow-up of 2 years, there was median PFS of 16.6 months vs 9.2 months respectively (HR, 0.76).
 

New Standard of Care for Patients with LS-SCLC

“This study had a very good safety profile,” said Dr. Spigel, who is also a medical oncologist and the chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, during his presentation.

“Looking at severe grade 3 or 4 events, these were nearly identical in either arm at 24%. Looking at any-grade immune-mediated AEs, these were 31.2% and 10.2% respectively, and then looking at radiation pneumonitis or pneumonitis, the rates were 38.2% in the durvalumab arm, compared with 30.2% in the placebo arm,” Dr. Spigel said.

Noting that there have been no major advances in the treatment of LS-SCLC for several decades, with most patients experiencing recurrences within 2 years of the cCRT standard of care, Dr. Spigel said “consolidation durvalumab will become the new standard of care for patients with LS-SCLC who have not progressed after cCRT.”

Toby Campbell, MD, a thoracic oncologist, who is professor and chief of Palliative Care at the University of Wisconsin, in Madison, Wisconsin, agrees.

“I take care of patients with small cell lung cancer, an aggressive cancer with high symptom burden that devastates patients and families in its wake,” said Dr. Campbell, during an interview. “About 15% of patients luckily present when the cancer is still contained in the chest and is potentially curable. However, with current treatments we give, which include chemotherapy together with radiation, we are ‘successful’ at curing one in four people.

“This study presents a new treatment option which makes a big difference to patients like mine,” Dr. Campbell continued. “For example, at the 2-year time point, nearly half of patients are still cancer-free. These folks have the opportunity to live their lives more fully, unburdened by the symptoms and dread this disease brings. If approved, I think this treatment would immediately be appropriate to use in clinic.

“Further, oncologists are comfortable using this medication as it is already FDA-approved and used similarly in non–small cell lung cancer.”

The study was funded by AstraZeneca. Dr. Spigel discloses consulting or advisory roles with Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Ipsen, Jazz Pharmaceuticals, Lyell Immunopharma, MedImmune, Monte Rosa Therapeutics, Novartis, Novocure, and Sanofi/Aventis. He has also received research funding from many companies, and travel, accommodations, and other expense reimbursements from AstraZeneca, Genentech, and Novartis.

Dr. Byers discloses honoraria from and consulting or advisory roles with Abbvie, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Beigene, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Genentech, Jazz Pharmaceuticals, Merck, Dohme, Novartis, and Puma Biotechnology. He also has received research funding from Amgen, AstraZeneca, and Jazz Pharmaceuticals.

Dr. Campbell has served as an advisor for Novocure and Genentech.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

Almost sixty percent of patients with macroscopic stage III melanoma who were randomized to 6 weeks of neoadjuvant immunotherapy needed no further treatment after therapeutic lymph node dissection in the phase 3 NADINA trial.

These results set a new standard of care in this patient population, the study’s lead author, Christian U. Blank, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Blank, a hematologist/oncologist from the Netherlands Cancer Institute in Amsterdam, called the result “very special,” noting that the trial included an active comparator, rather than a placebo control.

“When we treat these patients with surgery only, the outcome … is very bad: The 5-year relapse-free survival is only 30% and the overall survival is only 50%. Adjuvant therapy improves relapse-free survival but not overall survival ...Thus, there is an urgent need for these patients for novel therapy approaches,” he said during a press conference at the meeting.
 

Study Methods and Results

The study included 423 patients with stage III de novo or recurrent pathologically proven resectable melanoma with at least 1 lymph node metastasis. Patients were randomized to either the experimental neoadjuvant arm (n = 212), or the standard treatment control arm (n = 211), which consisted of therapeutic lymph node dissection (TLND) followed by 12 cycles of adjuvant nivolumab (NIVO 480 mg every 4 weeks).

Patients in the experimental arm received two cycles of neoadjuvant ipilimumab (IPI 80 mg every 3 weeks) plus NIVO 240 mg for 3 weeks followed by TLND. Those with a major pathologic response (MPR), defined as less than 10% vital tumor cells in the post-neoadjuvant resection specimen, went straight to follow-up.

Those without an MPR received adjuvant therapy. For patients with BRAF wild-type, this involved 11 cycles of adjuvant NIVO (480 mg every 4 weeks), while BRAF-mutated patients received dabrafenib plus trametinib (150 mg b.i.d./2 mg once a day; 46 weeks).

The study met its primary endpoint — event-free survival (EFS) — at the first interim analysis. After a median follow-up of 9.9 months, the estimated EFS was 83.7% for neoadjuvant immunotherapy versus 57.2% for standard of care, (P less than .0001, hazard ratio [HR] = 0.32).

“When we look into the subgroups, for example BRAF-mutated status or BRAF-wild-type status ... you see for both groups also a highly statistically significant outcome favoring the neoadjuvant therapy with hazard ratios of 0.29 and 0.35,” said Dr. Blank.

In total, 59% of patients in the experimental arm had an MPR needing no further treatment. “This is important, because the patients that achieve a major pathologic response have excellent outcomes, with an EFS of 95%,” said Dr. Blank.

He added that those with a partial response had an EFS of 76%, and among those who had “nonresponse,” the EFS was 57% — the same as that of patients in the control arm.

Toxicities were considered transient and acceptable, with systemic treatment-related grade 3 or 4 events in 29.7% of the neoadjuvant arm and 14.7% of the adjuvant arm.

NADINA is the first neoadjuvant checkpoint inhibitor phase 3 study in melanoma and the first phase 3 trial in oncology testing a checkpoint inhibitor without chemotherapy, noted Dr. Blank.

“At the moment we see only additions of immunotherapy to the chemotherapy neoadjuvant arms, but here you see that we can also treat patients with pure immunotherapy.”
 

Neoadjuvant Therapy Defined as Standard of Care

When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.

Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.

“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.

Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”

Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”

However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”

He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.

“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
 

EFS Improvement Exceeds Expectations

In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.

“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”

Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.

Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.

This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.

The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.

The study was funded by Bristol Myers-Squibb and the Australian government.

Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

A reformulation of the multiple cancer drugs in the combination treatment known as BEACOPP boosted progression free survival vs. the original therapy in adult patients with advanced-stage classical Hodgkin lymphoma, a large, open-label, phase III trial found.

At a median follow-up of 4 years, progression-free survival for the new treatment, known as BrECADD, was 94.3% vs. 90.9% for BEACOPP (hazard ratio, 0.66, 95% CI, P = .035), researchers led by Peter Borchmann, MD, assistant medical director of hematology and oncology at the University Hospital of Cologne, Germany, reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

“These results are really striking,” said hematologist-oncologist Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, who was not involved in the study and commented on it during an ASCO news briefing. “This is really poised to impact the standard-of-care treatment for patients with advanced-stage classical Hodgkin lymphoma.”

As Dr. Borchmann explained at the briefing, Hodgkin lymphoma is the most common cancer among young adults. “The median age at onset is around 30 years, and it can be primarily cured with chemotherapy. Intensified chemotherapy probably is better primary lymphoma control than less intensive treatment, but this comes at the cost of treatment-related adverse events.”

Dr. Borchmann and colleagues developed the existing treatment known as BEACOPP, a combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone. “It’s our standard of care due to its high primary cure rate, which is reflected by compelling progression-free survival,” he said.

However, he said, “it’s a high burden of treatment.” The investigational treatment, BrECADD, includes six drugs instead of seven: brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone. Two of the additions — brentuximab vedotin and dacarbazine — are cancer drugs, and dexamethasone is a steroid. There is one fewer cancer drug in the new formulation.

In the international HD21 trial (9 countries, 233 sites), researchers recruited patients aged 18-60 who received four or six cycles of either BEACOPP or BrECADD. The doses were guided by PET2 findings.

In the intention-to-treat cohort of 1,482 subjects (median age 31.1, 44% female), 742 were assigned to BrECADD and 740 to BEACOPP.

There were few early treatment failures in the BrECADD group vs. BEACOPP. The numbers who had primary progression within the first 3 months were 5 vs. 15, respectively, and the numbers reaching early relapse between months 3 and 12 were 11 vs. 23, respectively.

Four-year overall survival rates in the groups were nearly identical at 98.5% for BrECADD and 98.2% for BEACOPP. In regard to fertility, follicle-stimulating hormone recovery rates after 1 year were higher in the BrECADD group in both men (67% vs. 24%, respectively) and women (89% vs. 68%, respectively). Birth rates were also higher in the BrECADD group (n = 60 vs. n = 43 in the BEACOPP group).

Nearly two-thirds of those in BrECADD group (64%) required 12 weeks of therapy — four cycles. As for treatment-related morbidity toxicities, they were less common in the BrECADD group vs. the BEACOPP group (42% vs. 59%, respectively, P < .0001), and 1% of BrECADD-treated had them at 1 year.

Oncologist Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, welcomed the findings at the ACO news briefing. “By replacing some pretty toxic chemo with an antibody-drug conjugate [brentuximab vedotin], and changing the regimen a bit, and using PET scan to determine the number of cycles received, the long-term outcomes were maintained, if not even improved upon,” said Dr. Dr. Gralow, who was not involved in the study.

In addition, she said, the findings about fertility are good news because “these are young people who probably haven’t started a family yet, and we’re increasing the odds that they will be able to do so after survival.”

Moving forward, she said, “we will need to have some discussion on how this relates to ABVD, which is a more commonly used regimen in the United States right now.” ABVD refers to a combination of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine.

Takeda funded the study. Dr. Borchmann reported ties with BMS, GmbH & Co, Incyte, MSD/Merck, Roche, Takeda/Millennium, Miltenyi, Amgen, and Novartis. Some of the other study authors reported various disclosures. Dr. Odejide and Dr. Gralow have no disclosures.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

How does the presence of the JAK2 V617F mutation affect the diagnosis and classification of myeloproliferative neoplasms?

Dr. Richard: The JAK2 V617F mutation is found in > 90% of patients with polycythemia vera (PV). The remaining patients with PV have mutations in a different portion of the JAK2 gene. Since JAK2 mutations are found in virtually all patients with PV, having the mutation helps make the diagnosis, but does not carry prognostic significance. Some studies suggest that the allele burden of the mutated JAK2 V617F could be used to identify aggressive disease, but that finding is not universally accepted across all health care entities or practitioners. Variations in acceptance may be due to factors such as evolution of knowledge based on the latest evidence, clinical practice variability and priorities, availability of testing, and complexity of disease management.

This is not true of the 2 other classical myeloproliferative neoplasms (MPNs) that we see commonly in our clinics: essential thrombocytosis (ET) and myelofibrosis (MF). The CALR mutation can be seen in patients with ET and MF and signals a less aggressive form of the disease.

The presence of JAK2 V617F is critical for prognosis. Although it does not directly help to inform the patient of what to expect, identifying the mutation provides us with important information about the patient’s prognosis, which helps guide treatment decisions such as the intensity of therapy and monitoring for thrombotic events.

What are the potential implications of the JAK2 V617F mutation in the treatment of PV?

Dr. Richard: The discovery of the JAK2 V617F mutation in MPNs in 2005 led to the hope that perhaps there would be targeted therapy that could result in disease remissions. We had all hoped that the spectacular responses observed in patients with chronic myelogenous leukemia (CML) treated with imatinib could be replicated with JAK2 inhibitors. It turned out that blocking JAK2 was insufficient to reverse the disease. Studies are still ongoing whether drugs that can decrease the JAK2 V617F allele burden could be used to achieve a type of remission. Perhaps combination therapies will need to be developed.

I am hopeful that in the future we do see advancements that provide improved diagnosis and monitoring to help facilitate early detection, personalized treatment approaches to offer more effective and well tolerated therapies, risk stratification and prognostication to help identify higher risk progression, combination therapies to possibly improve efficacy and adherence, and novel therapeutic targets to help discover new treatments and provide improved outcomes.

How can JAK2 V617F lead to 3 different forms of myeloproliferative neoplasms?

Dr. Richard: The short answer is no one knows exactly. The phenotypic differences between PV and the other 2 MPN variants are most likely determined by the integration of other signaling pathways that are activated by the corresponding driver mutation, and interactions with other mutations. What also seems to matter is the sequence in which the individual mutations are acquired.

There have been documented cases of post-polycythemic leukemia that no longer have the JAK2 V617F mutation. However, at some point that mutation was lost, and the cells acquired other driver mutations that resulted in leukemia.

What we do know now is that there are several potential interactions that can coexist with JAK2 V617F. There is MPL mutation, which contributes to disease pathogenesis and thrombotic risk. Independent of JAK2 V617F pathways is CALR mutation, which is another driver of MPNs. In addition are other JAK mutations, epigenetic alterations, and microenvironmental factors. All of these have the potential to influence clinical manifestations by impacting clinical outcomes, affecting expression patterns and signaling inflammation within the bone marrow microenvironment.

Are there any ongoing research efforts or clinical trials exploring targeted therapies that specifically address the JAK2 V617F mutation in patients with PV?

Dr. Richard: The ongoing research efforts to address JAK2-targeted therapies are looking at options like novel JAK inhibitors, combination therapies, resistance mechanisms, improved safety profiles, biomarker identification, exploring new indications, and preclinical studies that involve the development and testing of new JAK inhibitors.

Other JAK2-targeted therapies continue to be in development. At this time, we have ruxolitinib, pacritinib, fedratinib, and momelotinib. None of them appear to be a magic bullet the way imatinib was with CML. Perhaps a better disease comparison is chronic lymphocytic leukemia (CLL). In CLL, targeted therapies against Bruton tyrosine kinase and BCL2 are being combined to result in many years of disease control. JAK2 inhibition may need to be combined with another active drug, perhaps against a mutation or pathway that has not yet been identified.

WASHINGTON — Eating within 3 hours of bedtime at least 4 days a week could increase chances for developing colorectal cancer, according to the results of research presented at the annual Digestive Disease Week^® (DDW).

Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.

“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”

Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.

So, what’s the possible connection between late eating and the risk for colorectal cancer?
 

Resetting Your Internal Clock

Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.

This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”

“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.

An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.

This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.

Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.

“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.

The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Eating within 3 hours of bedtime at least 4 days a week could increase chances for developing colorectal cancer, according to the results of research presented at the annual Digestive Disease Week^® (DDW).

Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.

“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”

Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.

So, what’s the possible connection between late eating and the risk for colorectal cancer?
 

Resetting Your Internal Clock

Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.

This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”

“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.

An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.

This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.

Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.

“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.

The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — Eating within 3 hours of bedtime at least 4 days a week could increase chances for developing colorectal cancer, according to the results of research presented at the annual Digestive Disease Week^® (DDW).

Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.

“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”

Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.

So, what’s the possible connection between late eating and the risk for colorectal cancer?
 

Resetting Your Internal Clock

Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.

This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”

“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.

An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.

This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.

Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.

“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.

The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.