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In ongoing efforts to investigate a link between vitamin D and colorectal cancer, new research shows that women who consume higher levels of vitamin D – particularly from dietary sources – have a reduced risk of developing early-onset colorectal cancer, compared with those who have lower levels.

This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.

Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.

“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.

Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
 

The evidence is in, but it’s incomplete

In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.

A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.

In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.

The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D₃ supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.

Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.

The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.

“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”

In animal models, vitamin D₃ is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.

Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.

“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D₃ can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
 

The hazards of a vitamin D deficiency

A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.

Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.

The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D₃) at 800-1,000 IU daily from dietary and supplemental sources.

Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.

In ongoing efforts to investigate a link between vitamin D and colorectal cancer, new research shows that women who consume higher levels of vitamin D – particularly from dietary sources – have a reduced risk of developing early-onset colorectal cancer, compared with those who have lower levels.

This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.

Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.

“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.

Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
 

The evidence is in, but it’s incomplete

In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.

A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.

In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.

The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D₃ supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.

Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.

The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.

“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”

In animal models, vitamin D₃ is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.

Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.

“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D₃ can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
 

The hazards of a vitamin D deficiency

A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.

Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.

The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D₃) at 800-1,000 IU daily from dietary and supplemental sources.

Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.

In ongoing efforts to investigate a link between vitamin D and colorectal cancer, new research shows that women who consume higher levels of vitamin D – particularly from dietary sources – have a reduced risk of developing early-onset colorectal cancer, compared with those who have lower levels.

This is according to an observational study published in the journal Gastroenterology. The study included 94,205 women (aged 25-42 years) who were followed between 1991 and 2015 during which 111 incident cases of early-onset colorectal cancer were diagnosed. Among 29,186 women who had at least one lower endoscopy from 1991 to 2011, 1,439 newly diagnosed conventional adenomas and 1,878 serrated polyps were found.

Women who consumed the highest average levels of total vitamin D of 450 IU per day, compared with those consuming less than 300 IU per day, showed a significantly reduced risk of early-onset colorectal cancer. Consuming 400 IU each day was associated with a 54% reduced risk of early-onset colorectal cancer.

“If confirmed, our findings could potentially lead to recommendations for higher vitamin D intake as an inexpensive low-risk complement to colorectal cancer screening as a prevention strategy for adults younger than age 50,” wrote the study authors, led by Edward L. Giovannucci, MD, ScD, of the Harvard School of Public Health, Boston.

Associations between vitamin D levels and colorectal cancer have been documented in review articles over the years. The link is the subject of 10 recently completed or ongoing clinical trials. Few studies have focused on early colorectal cancer and vitamin D intake. Unlike advanced colorectal cancer, the early-onset form of the disease is not as strongly associated with the traditional risk factors of a family history of colorectal cancer and it is therefore believed to be more strongly linked to other factors, such as lifestyle and diet – including vitamin D supplementation.
 

The evidence is in, but it’s incomplete

In addition to the new study in Gastroenterology, other observational studies, as well as laboratory and animal studies, suggest that vitamin D plays a role in inhibiting carcinogenesis. Vitamin D, researchers theorize, contains anti-inflammatory, immunomodulatory, and tumor angiogenesis properties that can slow the growth of tumors, but the evidence is mixed.

A meta-analysis of 137,567 patients published in 2013 in Preventive Medicine found an inverse association between 25-hydroxyvitamin D (25[OH]D) and total cancer mortality in women, but not among men. Three meta-analyses published in 2014 and 2019 found that vitamin D supplementation does not affect cancer incidence but does significantly reduce total cancer mortality rates by 12%-13%.

In 2019, researchers led by Marjorie McCullough, ScD, RD, senior scientific director of epidemiology research for the American Cancer Society, described a causal relationship between circulating vitamin D and colorectal cancer risk among 17 cohorts from a pooled analysis. “Our study suggests that optimal circulating 25(OH)D concentrations for colorectal cancer risk reduction are 75-100 nmol/L, [which is] higher than current Institute of Medicine recommendations for bone health,” she and colleagues wrote. Their findings were published in the Journal of the National Cancer Institute.

The Vitamin D and Omega-3 Trial (VITAL) published in 2019 in the New England Journal of Medicine, showed no significant effect of vitamin D₃ supplementation of 2,000 IU/day in lowering the risk of invasive cancer or cardiovascular events.

Despite the mixed results, studies offer valuable insights into cancer risks, said Scott Kopetz, MD, PhD, codirector of the colorectal cancer moon shot research program at the University of Texas MD Anderson Cancer Center, Houston.

The Gastroenterology study is noteworthy because it focuses on early-onset colorectal cancer, he said.

“[The authors] demonstrate for the first time that there is an association of vitamin D intake with early-onset colorectal incidence, especially in the left side of the colon and rectum where the increase in early onset colorectal cancer manifests,” Dr. Kopetz said. “The analysis suggests that it may require long-term vitamin D intake to derive the benefit, which may explain why some shorter-term randomized studies failed to demonstrate.”

In animal models, vitamin D₃ is “estimated to lower the incidence of colorectal cancer by 50%,” according to Lidija Klampfer, PhD, formerly a molecular biologist and senior research scientist with the Southern Research Institute, Birmingham, Ala.

Dr. Klampfer, a founding partner of ProteXase Therapeutics, is the author of an article on vitamin D and colon cancer published in 2014 in the World Journal of Gastrointestinal Oncology.

“The levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models,” she wrote. “Studies have shown that 1,25 dihydroxyvitamin D₃ can inhibit tumor-promoting inflammation leading to the development and progression of colon cancer.”
 

The hazards of a vitamin D deficiency

A severe vitamin D deficiency is associated with compromised bone and muscle health, calcium absorption, immunity, heart function and it can affect mood. Other studies have linked vitamin D deficiency to colorectal cancer, blood cancers, and bowel cancer.

Serum 25(OH)D is the primary circulating form of vitamin D and is considered the best marker for assessing vitamin D status, says Karin Amrein, MD, MSc, an endocrinologist with the Medical University of Graz (Austria). She was the lead author of a review on vitamin D deficiency published in January 2020 in the European Journal of Clinical Nutrition.

The Global Consensus Recommendations define vitamin D insufficiency as 12-20 ng/mL (30-50 nmol/L) and a deficiency as a serum 25OHD concentration less than 12 ng/mL (30 nmol/L). A deficiency in adults is usually treated with 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks followed by maintenance dosages of cholecalciferol (vitamin D₃) at 800-1,000 IU daily from dietary and supplemental sources.

Screening is recommended for individuals who exhibit symptoms and conditions associated with a vitamin D deficiency, but there is little agreement on recommended serum levels because every individual is different, according to the U.S. Preventive Services Task Force which updated its vitamin D recommendations in April for the first time in 7 years.

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

A new study suggests that tiny, clear nematodes can sniff out early-stage pancreatic cancer.

Research shows Caenorhabditis elegans are attracted to the odor certain chemicals give off – a behavior known as attractive chemotaxis – and early evidence indicates these scents may include human cancer cell secretions, cancer tissues, and urine from patients with colorectal, gastric, and breast cancers.

According to the recent analysis, published in Oncotarget, these small worms may be hot on the trail of pancreatic cancer–related compounds too. The researchers found that C. elegans were significantly more attracted to patients with early-stage pancreatic cancer versus healthy controls.

There is a huge need for research like this that explores strategies to detect pancreatic cancer early, but it’s far too soon to tell how, or if, this particular approach will be clinically relevant, according to Neeha Zaidi, MD, assistant professor of oncology and a medical oncologist specializing in pancreatic cancer at John Hopkins Medicine, Baltimore, who was not involved in the current analysis.

Right now, few diagnostic markers exist for identifying pancreatic ductal adenocarcinomas (PDACs), which account for 90% of pancreatic cancers. PDACs remain one of the deadliest cancers, with a 5-year survival rate of 9%.

A combination of surgical resection and chemotherapy is the only curative treatment, and just 20% of patients are eligible, Dr. Zaidi said. The majority are identified after the disease has metastasized.

However, patients’ 5-year survival rate improves markedly – as high as 85% – if the condition is caught sooner.

In the current study, the researchers first exposed C. elegans to the urine of 83 patients from cancer centers across Japan who had various stages of pancreatic cancer before and after undergoing surgical resection. Using an assay, which takes 30 minutes and 50-100 nematodes per test, C. elegans showed significantly higher chemotaxis toward preoperative urine, compared with postoperative urine.

In a second, closed-labeled arm, the nematodes were exposed to the urine of 28 randomized participants – 11 of whom had early-stage pancreatic cancer (0 or IA), plus 17 healthy volunteers. In this instance as well, C. elegans showed significantly higher chemotaxis in patients with early-stage pancreatic cancer, compared with healthy volunteers (P = .034). 

According to the authors, C. elegans “had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers.” And while this strategy needs to be further validated, they believe early detection of pancreatic cancer using C. elegans “can certainly be expected in the near future.”

The study aligns with previous research, showing that wild-type C. elegans are sensitive to scent and that these critters can smell cancer. Other studies have also found that sniffer canines can detect volatile organic compounds – including biomarkers of certain cancers – in the urine and breath of cancer patients. But training an adequate number of these canines for the clinic isn’t feasible, while C. elegans are far more compact and affordable.

According to Dr. Zaidi, a scent test using C. elegans “seems pretty feasible” and cost effective, but whether this approach will “change our care has yet to be determined.”

The authors, for instance, don’t specify how the scent test will be used, though Dr. Zaidi suspects it would be most relevant for following patients with a higher risk of pancreatic cancer. Alternatively, it could be used as a screening test, but that’s a massive undertaking and “this is way too early to tell if it’s going to be helpful to use this test on a broad scale,” Dr. Zaidi said.

To validate the approach, researchers would also need to know what exactly the C. elegans are smelling and to test it in a much larger number of patients, Dr. Zaidi said. The mere 11 patients with cancer in the blinded portion of the study are not sufficient to draw any major conclusions.

The study also claims a high sensitivity, but what about specificity, Dr. Zaidi said. In other words, are there a lot of false positives? 

In addition, a deeper look at the participants shows the two groups – early PDAC and healthy volunteers – were not adequately balanced. The median age of the diseased patients was 70, and the healthy volunteers was 39.

“This is a big difference,” Eithne Costello, PhD, professor of molecular oncology at Liverpool (England) University, said in an interview. “It [also] appears the controls are all of one sex (either all male or all female), while the cancer group is mixed.”

The authors attributed these shortcomings to the small population they had to work with: There simply aren’t many patients whose pancreatic cancer is detected early. Dr. Zaidi agreed that patients with pancreatic cancer stage 0 or IA are extremely difficult to come by.

Even still, researchers need to understand the mechanisms behind this approach and see it work in a much larger group of patients, Dr. Zaidi said.

The study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology. The authors reported institutional endowments received from Hirotsu Bio Science, Kinshu-kai Medical, IDEA Consultants, Ono Pharmaceutical, and others. Two coauthors are employees of Hirotsu Bio Science.

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

Adenoma miss rates were significantly lower with the use of an artificial intelligence (AI)–based computer-aided detection (CADe) system than with high-definition white light (HDWL), according to a new prospective, multicenter, single-blind randomized study based on data from more than 200 colonoscopies.

Missed adenomas can be generally categorized as adenomas fully obscured from the visual field or those appearing partly or fully in the visual field but missed by an endoscopist, wrote Jeremy R. Glissen Brown, MD, of Harvard Medical School, Boston, and colleagues. While retrospective and prospective studies in China, Italy, and Japan have shown that deep-learning CADe improves adenoma identification during colonoscopy, there have been no prospective U.S. studies on CADe in a diverse population, they noted.

In the study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 223 adults aged 22 years and older who underwent screening colonoscopies across four U.S. academic medical centers between 2019 and 2020. The procedure indication was primary colorectal cancer screening for 59.6% of the patients and postpolypectomy surveillance for 40.4%. Among this cohort, 45.3% (101) were female, 67.7% (151) were White, and 21% (133) were African American. Participants were randomized to receive either CADe colonoscopy first or HDWL colonoscopy first; the patients immediately underwent the other procedure in tandem fashion from the same endoscopist.

The primary outcome of the study was adenoma miss rate (AMR), defined as “the number of histologically confirmed adenomas detected during the second colonoscopy in either arm divided by the total number of adenomas detected during both procedures.” Sessile serrated lesion (SSL) miss rates and adenomas per colonoscopy (APC) were secondary outcomes.

Overall, the primary outcome of AMR was significantly lower in the CADe-first group, compared with the HDWL-first group (20.12% vs. 31.25%; P = .0247), with an odds ratio of 1.8048 (95% CI, 1.0780-3.0217). The CADe-first group yielded a lower SSL miss rate, compared with the HDLW-first group (7.14% vs. 42.11%; P = .0482), as well as a lower polyp miss rate (20.70% vs. 33.71%; P = .0007). The first-pass number of APC was significantly higher in the CADe-first group, compared with the HDWL-first group (1.19 [SD 2.03] vs. 0.90 [SD 1.55]; P = .0323). In addition, the first-pass adenoma detection rate (ADR) was not significantly different in the CADe-first group, compared with the HDWL-first group (50.44% vs. 43.64%; P = .3091), and the median withdrawal time was significantly shorter with CADe, compared with HDWL (9.5 minutes vs. 8.5 minutes; P = .0098).

There were no significant observable differences between the two groups regarding missed adenomas arranged by size or location. Moreover, there were no significant differences in miss rates for hyperplastic polyps or advanced adenomas. Factors significantly associated with missed adenomas included being in the HDLW-first group, age 65 years or younger, and the right colon vs. other locations. No immediate adverse events occurred in either group.

According to the researchers, while previous studies in China and Italy have shown increased ADR using CADe systems, these results are not generalizable to the U.S. population for several reasons, notably the studies’ inclusion of colonoscopy indications other than colorectal cancer screening and surveillance. Though the present study showed a significantly lower AMR with CADe, it still represents missed adenomas. The researchers note: “In the present study, in which CADe detected 285 polyps, there were only three false negatives (defined as polyps that were visualized by the endoscopist but not by the CADe system). Overall, this suggests that the ‘missed polyps’ in the CADe arm may have been obscured behind folds rather than in the visual field.” They added, “Further research is needed on combining CADe technologies with mucosal exposure devices, as the benefits of these tools for polyp detection may be additive.”

The study findings were limited by several factors, including the inability to detect a difference in overall ADR, the limited generalizability of the tandem study design to real-world practice, the inclusion of only experienced endoscopists, and the use of a second monitor that may have impacted gaze patterns, the researchers noted. However, the results represent the first examination of deep-learning CADe in a diverse U.S. population and showed a decrease in adenoma miss rates and decreased miss rates for polyps and SSLs, compared with HDWL. Based on these findings, the authors concluded CADe “has the potential to decrease inter-provider variability in colonoscopy quality by reducing adenoma miss rate even in experienced providers.”
 

Reducing miss rates matters

“Missed adenomas can be associated with the development of interval colorectal cancer, so whether novel technologies such as artificial intelligence-based computer-aided polyp detection system can decrease adenoma miss rate is of interest,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr Sakuraba said he was not surprised by the current study findings, as several pilot and randomized studies have shown the benefits of AI-based polyp detection systems. As for how the AI-assisted technology might improve practice, he said it may be a valuable addition. “Adenoma miss rate was significantly lower with an AI-based polyp detection system, so it might lead to decreased colorectal cancer,” he explained. “Various methods to improve adenoma detection should complement each other. 

Dr. Sakuraba also commented that additional research is needed outside of academic centers, noting “further studies in the community setting involving various endoscopists are required to confirm generalizability.”

Lead author Dr. Glissen Brown had no financial conflicts to disclose. This was an investigator-initiated study, with research software and study funding provided by Wision. Dr. Sakuraba disclosed collaborative research with Fuji film, which was not involved in this study.

Adenoma miss rates were significantly lower with the use of an artificial intelligence (AI)–based computer-aided detection (CADe) system than with high-definition white light (HDWL), according to a new prospective, multicenter, single-blind randomized study based on data from more than 200 colonoscopies.

Missed adenomas can be generally categorized as adenomas fully obscured from the visual field or those appearing partly or fully in the visual field but missed by an endoscopist, wrote Jeremy R. Glissen Brown, MD, of Harvard Medical School, Boston, and colleagues. While retrospective and prospective studies in China, Italy, and Japan have shown that deep-learning CADe improves adenoma identification during colonoscopy, there have been no prospective U.S. studies on CADe in a diverse population, they noted.

In the study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 223 adults aged 22 years and older who underwent screening colonoscopies across four U.S. academic medical centers between 2019 and 2020. The procedure indication was primary colorectal cancer screening for 59.6% of the patients and postpolypectomy surveillance for 40.4%. Among this cohort, 45.3% (101) were female, 67.7% (151) were White, and 21% (133) were African American. Participants were randomized to receive either CADe colonoscopy first or HDWL colonoscopy first; the patients immediately underwent the other procedure in tandem fashion from the same endoscopist.

The primary outcome of the study was adenoma miss rate (AMR), defined as “the number of histologically confirmed adenomas detected during the second colonoscopy in either arm divided by the total number of adenomas detected during both procedures.” Sessile serrated lesion (SSL) miss rates and adenomas per colonoscopy (APC) were secondary outcomes.

Overall, the primary outcome of AMR was significantly lower in the CADe-first group, compared with the HDWL-first group (20.12% vs. 31.25%; P = .0247), with an odds ratio of 1.8048 (95% CI, 1.0780-3.0217). The CADe-first group yielded a lower SSL miss rate, compared with the HDLW-first group (7.14% vs. 42.11%; P = .0482), as well as a lower polyp miss rate (20.70% vs. 33.71%; P = .0007). The first-pass number of APC was significantly higher in the CADe-first group, compared with the HDWL-first group (1.19 [SD 2.03] vs. 0.90 [SD 1.55]; P = .0323). In addition, the first-pass adenoma detection rate (ADR) was not significantly different in the CADe-first group, compared with the HDWL-first group (50.44% vs. 43.64%; P = .3091), and the median withdrawal time was significantly shorter with CADe, compared with HDWL (9.5 minutes vs. 8.5 minutes; P = .0098).

There were no significant observable differences between the two groups regarding missed adenomas arranged by size or location. Moreover, there were no significant differences in miss rates for hyperplastic polyps or advanced adenomas. Factors significantly associated with missed adenomas included being in the HDLW-first group, age 65 years or younger, and the right colon vs. other locations. No immediate adverse events occurred in either group.

According to the researchers, while previous studies in China and Italy have shown increased ADR using CADe systems, these results are not generalizable to the U.S. population for several reasons, notably the studies’ inclusion of colonoscopy indications other than colorectal cancer screening and surveillance. Though the present study showed a significantly lower AMR with CADe, it still represents missed adenomas. The researchers note: “In the present study, in which CADe detected 285 polyps, there were only three false negatives (defined as polyps that were visualized by the endoscopist but not by the CADe system). Overall, this suggests that the ‘missed polyps’ in the CADe arm may have been obscured behind folds rather than in the visual field.” They added, “Further research is needed on combining CADe technologies with mucosal exposure devices, as the benefits of these tools for polyp detection may be additive.”

The study findings were limited by several factors, including the inability to detect a difference in overall ADR, the limited generalizability of the tandem study design to real-world practice, the inclusion of only experienced endoscopists, and the use of a second monitor that may have impacted gaze patterns, the researchers noted. However, the results represent the first examination of deep-learning CADe in a diverse U.S. population and showed a decrease in adenoma miss rates and decreased miss rates for polyps and SSLs, compared with HDWL. Based on these findings, the authors concluded CADe “has the potential to decrease inter-provider variability in colonoscopy quality by reducing adenoma miss rate even in experienced providers.”
 

Reducing miss rates matters

“Missed adenomas can be associated with the development of interval colorectal cancer, so whether novel technologies such as artificial intelligence-based computer-aided polyp detection system can decrease adenoma miss rate is of interest,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr Sakuraba said he was not surprised by the current study findings, as several pilot and randomized studies have shown the benefits of AI-based polyp detection systems. As for how the AI-assisted technology might improve practice, he said it may be a valuable addition. “Adenoma miss rate was significantly lower with an AI-based polyp detection system, so it might lead to decreased colorectal cancer,” he explained. “Various methods to improve adenoma detection should complement each other. 

Dr. Sakuraba also commented that additional research is needed outside of academic centers, noting “further studies in the community setting involving various endoscopists are required to confirm generalizability.”

Lead author Dr. Glissen Brown had no financial conflicts to disclose. This was an investigator-initiated study, with research software and study funding provided by Wision. Dr. Sakuraba disclosed collaborative research with Fuji film, which was not involved in this study.

Adenoma miss rates were significantly lower with the use of an artificial intelligence (AI)–based computer-aided detection (CADe) system than with high-definition white light (HDWL), according to a new prospective, multicenter, single-blind randomized study based on data from more than 200 colonoscopies.

Missed adenomas can be generally categorized as adenomas fully obscured from the visual field or those appearing partly or fully in the visual field but missed by an endoscopist, wrote Jeremy R. Glissen Brown, MD, of Harvard Medical School, Boston, and colleagues. While retrospective and prospective studies in China, Italy, and Japan have shown that deep-learning CADe improves adenoma identification during colonoscopy, there have been no prospective U.S. studies on CADe in a diverse population, they noted.

In the study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 223 adults aged 22 years and older who underwent screening colonoscopies across four U.S. academic medical centers between 2019 and 2020. The procedure indication was primary colorectal cancer screening for 59.6% of the patients and postpolypectomy surveillance for 40.4%. Among this cohort, 45.3% (101) were female, 67.7% (151) were White, and 21% (133) were African American. Participants were randomized to receive either CADe colonoscopy first or HDWL colonoscopy first; the patients immediately underwent the other procedure in tandem fashion from the same endoscopist.

The primary outcome of the study was adenoma miss rate (AMR), defined as “the number of histologically confirmed adenomas detected during the second colonoscopy in either arm divided by the total number of adenomas detected during both procedures.” Sessile serrated lesion (SSL) miss rates and adenomas per colonoscopy (APC) were secondary outcomes.

Overall, the primary outcome of AMR was significantly lower in the CADe-first group, compared with the HDWL-first group (20.12% vs. 31.25%; P = .0247), with an odds ratio of 1.8048 (95% CI, 1.0780-3.0217). The CADe-first group yielded a lower SSL miss rate, compared with the HDLW-first group (7.14% vs. 42.11%; P = .0482), as well as a lower polyp miss rate (20.70% vs. 33.71%; P = .0007). The first-pass number of APC was significantly higher in the CADe-first group, compared with the HDWL-first group (1.19 [SD 2.03] vs. 0.90 [SD 1.55]; P = .0323). In addition, the first-pass adenoma detection rate (ADR) was not significantly different in the CADe-first group, compared with the HDWL-first group (50.44% vs. 43.64%; P = .3091), and the median withdrawal time was significantly shorter with CADe, compared with HDWL (9.5 minutes vs. 8.5 minutes; P = .0098).

There were no significant observable differences between the two groups regarding missed adenomas arranged by size or location. Moreover, there were no significant differences in miss rates for hyperplastic polyps or advanced adenomas. Factors significantly associated with missed adenomas included being in the HDLW-first group, age 65 years or younger, and the right colon vs. other locations. No immediate adverse events occurred in either group.

According to the researchers, while previous studies in China and Italy have shown increased ADR using CADe systems, these results are not generalizable to the U.S. population for several reasons, notably the studies’ inclusion of colonoscopy indications other than colorectal cancer screening and surveillance. Though the present study showed a significantly lower AMR with CADe, it still represents missed adenomas. The researchers note: “In the present study, in which CADe detected 285 polyps, there were only three false negatives (defined as polyps that were visualized by the endoscopist but not by the CADe system). Overall, this suggests that the ‘missed polyps’ in the CADe arm may have been obscured behind folds rather than in the visual field.” They added, “Further research is needed on combining CADe technologies with mucosal exposure devices, as the benefits of these tools for polyp detection may be additive.”

The study findings were limited by several factors, including the inability to detect a difference in overall ADR, the limited generalizability of the tandem study design to real-world practice, the inclusion of only experienced endoscopists, and the use of a second monitor that may have impacted gaze patterns, the researchers noted. However, the results represent the first examination of deep-learning CADe in a diverse U.S. population and showed a decrease in adenoma miss rates and decreased miss rates for polyps and SSLs, compared with HDWL. Based on these findings, the authors concluded CADe “has the potential to decrease inter-provider variability in colonoscopy quality by reducing adenoma miss rate even in experienced providers.”
 

Reducing miss rates matters

“Missed adenomas can be associated with the development of interval colorectal cancer, so whether novel technologies such as artificial intelligence-based computer-aided polyp detection system can decrease adenoma miss rate is of interest,” said Atsushi Sakuraba, MD, of the University of Chicago, in an interview.

Dr Sakuraba said he was not surprised by the current study findings, as several pilot and randomized studies have shown the benefits of AI-based polyp detection systems. As for how the AI-assisted technology might improve practice, he said it may be a valuable addition. “Adenoma miss rate was significantly lower with an AI-based polyp detection system, so it might lead to decreased colorectal cancer,” he explained. “Various methods to improve adenoma detection should complement each other. 

Dr. Sakuraba also commented that additional research is needed outside of academic centers, noting “further studies in the community setting involving various endoscopists are required to confirm generalizability.”

Lead author Dr. Glissen Brown had no financial conflicts to disclose. This was an investigator-initiated study, with research software and study funding provided by Wision. Dr. Sakuraba disclosed collaborative research with Fuji film, which was not involved in this study.

In the first study of its kind, women with a breast cancer diagnosis who recalled eating nuts were found to have a significantly better disease-free survival over a 10-year study period, compared with those who said they had not eaten nuts.

PxHere

There was also an improvement in overall survival, but this was not statistically significant.

The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis. 

The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.

“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.

“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.

However, as with all observational studies, this report shows an association and not causation.

“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.  

The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.

Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.

Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.

Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.

She also offered some general advice about eating nuts.  

“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.

A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”

The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.

“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
 

Study authors did an adjusted analysis

The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.

Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.

An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.

Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.

However, the two groups had many differences, as noted by the authors and outside experts.

The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.

So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.

Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).

The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.

The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.

Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.

The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.

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

In the first study of its kind, women with a breast cancer diagnosis who recalled eating nuts were found to have a significantly better disease-free survival over a 10-year study period, compared with those who said they had not eaten nuts.

PxHere

There was also an improvement in overall survival, but this was not statistically significant.

The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis. 

The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.

“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.

“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.

However, as with all observational studies, this report shows an association and not causation.

“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.  

The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.

Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.

Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.

Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.

She also offered some general advice about eating nuts.  

“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.

A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”

The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.

“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
 

Study authors did an adjusted analysis

The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.

Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.

An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.

Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.

However, the two groups had many differences, as noted by the authors and outside experts.

The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.

So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.

Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).

The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.

The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.

Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.

The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.

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

In the first study of its kind, women with a breast cancer diagnosis who recalled eating nuts were found to have a significantly better disease-free survival over a 10-year study period, compared with those who said they had not eaten nuts.

PxHere

There was also an improvement in overall survival, but this was not statistically significant.

The finding comes from a study of more than 3,000 patients conducted in China, published online in the International Journal of Cancer. Patients were queried about nut consumption on only one occasion, 5 years after their breast cancer diagnosis. 

The investigators report a dose-response pattern between nut eating and the risk of both breast cancer recurrence and overall mortality, with those consuming the largest amounts having the lowest risks.

“Nuts are important components of healthy diets. Promoting this modifiable lifestyle factor should be emphasized in breast cancer survivor guidelines,” conclude Xiao-Ou Shu, MD, PhD, of Vanderbilt University, Nashville, Tenn., and colleagues in the study.

“The association for disease-free survival is quite strong and robust,” Dr. Shu told this news organization.

However, as with all observational studies, this report shows an association and not causation.

“Based upon this study alone, the evidence is weak,” said Wendy Chen, MD, MPH, a breast oncologist at Dana-Farber Cancer Institute in Boston, who was approached for comment.  

The people who consumed nuts generally had more education, higher income, lower body mass index, earlier-stage cancers, and more physically active lives – all factors associated with better breast cancer survival, she observed. “The authors tried to control for these factors,” Dr. Chen acknowledged. But it’s hard to know whether nut consumption was “truly” the difference maker, she said.

Furthermore, the study population is also “a bit unusual” because people had to survive 5 years after diagnosis to be included in the analysis – and thus is not representative of breast cancer survivors, she noted.

Erin Van Blarigan, PhD, an epidemiologist at the University of California, San Francisco, described the overall evidence of the beneficial relationship between nut eating and breast cancer – including this study – as “limited.” She previously led a study that observed benefits of nut intake for patients with colon cancer.

Dr. Van Blarigan also noted that nut intake in this study was “very low” – with the median intake less than one serving per week.

She also offered some general advice about eating nuts.  

“Nuts are an energy-dense food, so portion sizes should be kept small,” she said, explaining a portion should be about 1 ounce or 1/4 cup of nuts or 1-2 tablespoons of nut butter.

A little may go a long way, she suggested, as research to date “suggests only small amounts may be needed to gain potential benefits.”

The level of nut consumption was low in the Chinese study population (median = 17.3 grams/week) compared with the 42.5 grams/week recommended by the American Heart Association, the study authors acknowledge.

“Nuts, particularly tree nuts, are expensive in China. Traditionally, nut consumption level has been low among Chinese, particularly in the old generation,” commented Dr. Shu.
 

Study authors did an adjusted analysis

The new study was conducted among 3,449 participants of the Shanghai Breast Cancer Survival Study.

Nut consumption (including peanuts and tree nuts such as walnuts) was assessed with a food questionnaire at 5 years post-diagnosis.

An analysis was conducted at 10 years post-diagnosis (and 5 years after the diet questionnaire). At this 10-year mark, there were 252 breast cancer-specific deaths. Among 3,274 survivors without previous recurrence at the dietary assessment, 209 went on to develop breast cancer-specific events – either recurrence, metastasis, or breast cancer mortality.

Nut consumers had higher overall survival (93.7% vs. 89%; P = .003) and disease-free survival (94.1% vs. 86.2%; P <.001) rates than nonconsumers.

However, the two groups had many differences, as noted by the authors and outside experts.

The consumers had a younger age at diagnosis, lower BMI, higher total energy intake, higher diet quality score, and higher soy food intake. In addition, nut consumers were more likely to have a higher education, personal income, and physical activity level (≥7.5 metabolic equivalent of task-hour/week) as well as to have received immunotherapy.

So the investigators adjusted for many of those variables and found that nut consumption was associated with significantly better disease-free survival (hazard ratio, 0.52; 95% confidence interval, 0.35-0.75), but a nonsignificantly improved overall survival (HR, 0.90; 95% CI, 0.66-1.23), as noted above.

Analyses by amount of nut intake showed a dose-response relationship for both overall survival (P trend = .022) and disease-free survival (P trend = .003).

The authors say that “there has been no strong evidence to support individual food items in favor of breast cancer survival,” citing a 2018 report entitled “Diet, Nutrition, Physical Activity and Breast Cancer Survivors” from the World Cancer Research Fund/American Institute for Cancer Research.

The new study provides evidence that nuts may be such a food, they say, while also calling for studies to confirm their findings.

Study limitations include that fact that the statuses of recurrence and metastasis were self-reported. Misclassification, particularly regarding the event date, is likely, the team says.

The study authors and Dr. Van Blarigan and Dr. Chen have disclosed no relevant financial relationships.

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

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

Targeted agents for the treatment of diffuse large B-cell lymphoma (DLBCL) should be used in the context of oncogenic addictions within the lymphoma cells, and a thorough molecular analysis should be conducted prior to using specific agents, a review of the relevant literature suggests.

“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.

Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.

The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”

The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.

“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.

The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:

–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.

In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.

–Results have been mixed with PI3K inhibitors.

Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.

Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.

Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”

Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.

“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.

Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.

–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.

In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.

The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.

“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.

In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.

“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”

Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.

For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.

This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.

[email protected]

Targeted agents for the treatment of diffuse large B-cell lymphoma (DLBCL) should be used in the context of oncogenic addictions within the lymphoma cells, and a thorough molecular analysis should be conducted prior to using specific agents, a review of the relevant literature suggests.

“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.

Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.

The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”

The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.

“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.

The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:

–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.

In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.

–Results have been mixed with PI3K inhibitors.

Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.

Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.

Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”

Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.

“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.

Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.

–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.

In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.

The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.

“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.

In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.

“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”

Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.

For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.

This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.

[email protected]

Targeted agents for the treatment of diffuse large B-cell lymphoma (DLBCL) should be used in the context of oncogenic addictions within the lymphoma cells, and a thorough molecular analysis should be conducted prior to using specific agents, a review of the relevant literature suggests.

“In addition ... single-agent regimens are most likely not efficient enough to substantially improve the outcome of patients with DLBCL,” Wendan Xu and colleagues at University Hospital Munster, Germany, concluded, based on their review.

Indeed, novel combinations that include B-cell receptor (BCR) signaling and phosphatidylinositol 3-kinase (PI3K) inhibitors are needed for DLBCL treatment, and treatment should also include conventional chemoimmunotherapeutic regimens as well as other targeted agents and novel immunologic approaches, they wrote. Such novel combinations could overcome mechanisms of resistance and increase cure rates in individuals with DLBCL, they contended.

The authors’ observations are based on a search of the available data, from which they summarized the “current understanding of BCR signaling with a special focus on the PI3K pathway and its role in the pathogenesis of DLBCL.”

The addition of the anti-CD20 antibody rituximab to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) significantly improved outcomes for patients with DLBCL, but about a third of patients are not cured by the rituximab-CHOP (R-CHOP) regimen and subsequent therapies, they said, explaining their rationale for the review.

“A better understanding of the molecular pathogenesis is warranted to use novel targeted agents in an optimal manner,” they said.

The authors also addressed clinical implications of the findings, and mechanisms of resistance to PI3k inhibitors. For example, they noted that:

–Bruton’s tyrosine kinase (BTK) inhibitors may be beneficial when added to R-CHOP.

In the randomized phase 3 PHOENIX trial, ibrutinib plus R-CHOP versus R-CHOP alone in patients with non–germinal center B-cell (non-GCB) DLBCL showed a survival benefit in patients over 60 years of age, which suggests a possible role for “an intensified R-CHOP regimen that includes a BTK inhibitor” in these patients, they said. They added that confirmatory trials are under way, including the ESCALADE trial looking at the second-generation BTK inhibitor acalabrutinib combined with R-CHOP versus R-CHOP alone in patients with untreated DLBCL.

–Results have been mixed with PI3K inhibitors.

Various PI3K inhibitors have been evaluated for the treatment of patients with DLBCL.

Idelalisib, a first-in-class PI3K-specific inhibitor approved for treatment of relapsed/refractory (r/r) follicular lymphoma, small lymphocytic lymphoma, and chronic lymphocytic leukemia (CLL), showed only modest activity in preclinical DLBCL models, and no responses were detectable in a small trial of patients with r/r DLBCL, the authors said. “Severe toxic side effects and treatment-related deaths occurred in several clinical trials that tested idelalisib in combination with antibodies alone or with antibodies and chemotherapy, leading to the premature discontinuation of some of these studies,” they noted.

Other studies investigating idelalisib plus lenalidomide and rituximab or the spleen tyrosine kinase (SYK) inhibitor entospletinib in patients with r/r CLL or lymphoma were also halted because of “overwhelming, immune-mediated pulmonary and/or hepatic toxicities.”

Copanlisib, an intravenous pan-class I PI3K inhibitor with preferential inhibition of PI3Ka and PI3Kd, showed some promise as monotherapy in a phase 2 trial of patients with r/r DLBCL. The overall response rate was about 20%, and response was “numerically higher” in activated B-cell like (ABC) DLBCL, compared with GCB DLBCL (32% vs. 13%), confirming preclinical data that showed PI3Ka/d inhibition effectiveness mainly in ABC DLBCL.

“Compared with idelalisib, copanlisib appears to have a more favorable toxicity profile, with a lower incidence of severe complications,” they said, adding that a phase 2 trial of copanlisib plus R-CHOP as first-line therapy for patients with DLBCL is under way.

Further, monotherapy with buparlisib, a pan-class I PI3K inhibitor, was associated with a low response rate of 11.5% in a DLBCL subcohort in a phase 2 study, whereas parsaclisib, a next-generation inhibitor with specificity to the PI3Kd isoform, showed efficacy as a monotherapy in patients with r/r DLBCL in a phase 2 study (overall response rate, 25.5%), they said, adding that other PI3K inhibitors with additional inhibitory effects are under clinical development.

–Various molecular mechanisms of resistance to PI3K inhibitors have been described preclinically and clinically.

In an unbiased exploratory analysis of samples from patients treated with copanlisib, a 16-gene mutation signature that separated responders from nonresponders was identified, the authors said.

The finding suggests that genetic aberrations dictate response to PI3K inhibitors, they noted.

“This 16-gene signature included TNFAIP3, CREBBP, and PRDM1, which are known to be important in the molecular pathogenesis of DLBCL,” they wrote. A composite score was developed to reflect the numerical presence or absence of mutations in the gene set, they explained, adding that patients with a high composite score had a significantly higher overall response rate and longer progression-free survival than did patients with a lower score.

In addition, idelalisib treatment resulted in a feedback activation of PI3Ka in ABC DLBCL cells.

“This rebound of PI3K activity was overcome by subsequent PI3Ka inhibition in preclinical DLBCL models, further underscoring the necessity of inhibiting both PI3Ka and PI3Kd to achieve responses in ABC DLBCL,” they wrote, adding that “[i]n ABC DLBCL models treated with the PI3Ka/PI3Kd inhibitor AZD8835, activated CARD11 mutations were identified as a mechanism of resistance.”

Investigations looking at various treatment combinations to overcome resistance to PI3K inhibition and improve the efficacy of targeted approaches are under way, they said.

For example, copanlisib plus the BCL-2 inhibitor venetoclax showed “synergistic activity in BCR-dependent DLBCLs, with genetic bases for BCL-2 dysregulation in vitro and in vivo,” and combination treatment with umbralisib and the proteasome inhibitor carfilzomib showed synergistic cytotoxicity in B-cell lymphoma, they said, noting that the latter combination is currently being evaluated in patients with DLBCL.

This work was supported by a research grant from the Deutsche Krebshilfe. Dr. Xu reported having no financial disclosures.

[email protected]

FROM JAMA ONCOLOGY

Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.

“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.

“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”

Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients. 

“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.

In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.

“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.

This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival  (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.

“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.

“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.

Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.

Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.

“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.

No relevant conflicts of interest were reported for this research.

FROM JAMA ONCOLOGY

Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.

“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.

“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”

Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients. 

“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.

In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.

“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.

This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival  (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.

“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.

“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.

Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.

Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.

“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.

No relevant conflicts of interest were reported for this research.

FROM JAMA ONCOLOGY

Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.

“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.

“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”

Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients. 

“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.

In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.

“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.

This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival  (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.

“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.

“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.

Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.

Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.

“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.

No relevant conflicts of interest were reported for this research.

In patients with unresectable or metastatic hepatocellular carcinoma (HCC), donafenib was superior to sorafenib in improving overall survival (OS), according to a head-to-head study published in the Journal of Clinical Oncology. This novel multikinase inhibitor and deuterated sorafenib derivative also showed improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.

“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.

Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.

This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority. 

Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”

Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.

“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”

Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.

In patients with unresectable or metastatic hepatocellular carcinoma (HCC), donafenib was superior to sorafenib in improving overall survival (OS), according to a head-to-head study published in the Journal of Clinical Oncology. This novel multikinase inhibitor and deuterated sorafenib derivative also showed improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.

“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.

Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.

This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority. 

Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”

Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.

“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”

Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.

In patients with unresectable or metastatic hepatocellular carcinoma (HCC), donafenib was superior to sorafenib in improving overall survival (OS), according to a head-to-head study published in the Journal of Clinical Oncology. This novel multikinase inhibitor and deuterated sorafenib derivative also showed improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.

“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.

Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.

This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority. 

Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”

Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.

“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”

Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.

Approximately one-third of colonoscopies with inadequate bowel preparation were repeated within 1 year despite current guidelines, according to data from a new study of more than 260,000 procedures.

Eraxion/Thinkstock

Previous studies have shown that poor bowel prep, which occurs in approximately 25% of colonoscopies, can lead to lesion miss rates of as much as 42%-48%, Audrey H. Calderwood, MD, an associate professor of medicine at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues wrote. However, factors affecting recommendations for repeat colonoscopies following poor bowel prep have not been examined.

In the study, published in Gastrointestinal Endoscopy, the researchers conducted a cross-sectional retrospective analysis of 260,314 colonoscopies reported to the GI Quality Improvement Consortium (GIQuIC) from 2011 to 2018. The review included adults aged 50-75 years in whom bowel preparation was deemed inadequate. The GIQuIC database defines adequate bowel preparation as “sufficient to accurately detect polyps greater than 5 mm in size,” the researchers noted. The procedures in this study were performed at 672 sites by 4,001 endoscopists, and the primary outcome was a recommendation for a repeat colonoscopy within 1 year.

In 31.9% of the procedures, the recommended follow-up interval for repeat colonoscopy was within 1 year, and there were no significant differences according to indication for the procedures (32.3% of screening and 31.2% of surveillance). Of these, 54.9% of patients received a follow-up interval of 1 year and 24.7% a follow-up interval within 3 months. Only 2.4% were advised they required no follow-up procedure.

The researchers found that patients with more severe disease had a higher likelihood of receiving a recommendation for follow-up colonoscopy within 1 year – 84% with adenocarcinoma, 51.8% with advanced lesions, and 23.2% with one to two small adenomas.

In the multivariate analysis, there were specific patient factors significantly associated with 1-year follow-up recommendations. The researchers found patients aged 70-75 years were less likely than younger patients (adjusted odds ratio, 0.96; 95% confidence interval, 0.93-0.98) to receive a 1-year follow-up recommendation; men were more likely than women (aOR, 1.04; 95% CI, 1.02-1.06) to receive a 1-year follow-up recommendation; and patients with adenocarcinoma findings more likely to receive a 1-year follow-up recommendation compared to those with no adenocarcinoma (aOR, 10.43; 95% CI, 7.77-13.98). In addition, they found patients residing in the Northeast and those whose procedure was performed by an endoscopist with an adenoma detection rate of at least25% were more likely to receive recommendations for a repeat colonoscopy within 1 year.

“The recommendation for repeat screening or surveillance colonoscopy within 1 year when the index colonoscopy has an inadequate bowel preparation is currently a quality measure in gastroenterology,” the researchers noted. “Although our study period started in 2011, when we looked at the time period of 2014 to 2018, which is after publication of guidelines of when to repeat colonoscopy after inadequate bowel preparation, there were still low rates of guideline-concordant recommendations.”

These overall low rates, which are consistent with other studies, may be due uncertainty on the part of the endoscopist in determining inadequate bowel prep based on evolving guidelines, the researchers noted. However, the higher frequency of recommendations for repeat procedures within 1 year for patients with advanced disease suggests that endoscopists are taking pathology into account.

The study findings were limited by several factors, including the lack of standardized assessment of bowel prep quality, variation in descriptions of bowel cleanliness, and lack of information on the primary factor in follow-up recommendations. However, the results were strengthened by the large sample size, the inclusion of multiple sites and providers, and the low volume of timely repeat procedures, which has clinical implications in terms of missed lesions, “including potential interval CRC [colorectal cancer],” the researchers said.
 

Get the word out on describing preps and planning follow-ups

The current study is important because it highlights that, even when endoscopists have a reasonable understanding on how to set follow-up intervals for polyp follow-up, what to do with a patient who comes in poorly prepped is more of a problem, Kim L. Isaacs, MD, of the University of North Carolina at Chapel Hill, said in an interview.

Dr Isaacs said she was not surprised by the study findings. “There are all gradations of inadequate preps that limit visualization in different ways, and there are many ways of recording this on procedure reports. The findings in the current study emphasize several points. The first is that the recommendation of following up an inadequate or poor prep in a year needs to be widely disseminated. The second is that there needs to be more education on standardization on how preps are described. In some poor preps, much of the colon can be seen, and clinicians can identify polyps 5-6 mm, so a 1-year follow-up may not be needed.” This type of research is challenging if the data are not standardized, she added. 

Dr. Isaacs agreed with the authors’ description of repeat colonoscopies after poor bowel prep as a quality improvement area given the variability in following current recommendations, which leads into next steps for research.

“Understanding reasons for the recommendations that endoscopists made for follow-up would be the next step in this type of research,” Dr Isaacs noted. “After that, studies on the impact of an educational intervention, followed by repeating the initial assessment.”

The study received no outside funding. The researchers had no financial conflicts to disclose; however, lead author Dr. Calderwood disclosed support from the National Cancer Institute, the Dartmouth-Hitchcock Cancer Research Fellows Program, the Dartmouth-Hitchcock Norris Cotton Cancer Center, and the Dartmouth Clinical and Translational Science Institute. Dr Isaacs had no financial conflicts to disclose but has previously served on the editorial board of GI & Hepatology News.

Approximately one-third of colonoscopies with inadequate bowel preparation were repeated within 1 year despite current guidelines, according to data from a new study of more than 260,000 procedures.

Eraxion/Thinkstock

Previous studies have shown that poor bowel prep, which occurs in approximately 25% of colonoscopies, can lead to lesion miss rates of as much as 42%-48%, Audrey H. Calderwood, MD, an associate professor of medicine at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues wrote. However, factors affecting recommendations for repeat colonoscopies following poor bowel prep have not been examined.

In the study, published in Gastrointestinal Endoscopy, the researchers conducted a cross-sectional retrospective analysis of 260,314 colonoscopies reported to the GI Quality Improvement Consortium (GIQuIC) from 2011 to 2018. The review included adults aged 50-75 years in whom bowel preparation was deemed inadequate. The GIQuIC database defines adequate bowel preparation as “sufficient to accurately detect polyps greater than 5 mm in size,” the researchers noted. The procedures in this study were performed at 672 sites by 4,001 endoscopists, and the primary outcome was a recommendation for a repeat colonoscopy within 1 year.

In 31.9% of the procedures, the recommended follow-up interval for repeat colonoscopy was within 1 year, and there were no significant differences according to indication for the procedures (32.3% of screening and 31.2% of surveillance). Of these, 54.9% of patients received a follow-up interval of 1 year and 24.7% a follow-up interval within 3 months. Only 2.4% were advised they required no follow-up procedure.

The researchers found that patients with more severe disease had a higher likelihood of receiving a recommendation for follow-up colonoscopy within 1 year – 84% with adenocarcinoma, 51.8% with advanced lesions, and 23.2% with one to two small adenomas.

In the multivariate analysis, there were specific patient factors significantly associated with 1-year follow-up recommendations. The researchers found patients aged 70-75 years were less likely than younger patients (adjusted odds ratio, 0.96; 95% confidence interval, 0.93-0.98) to receive a 1-year follow-up recommendation; men were more likely than women (aOR, 1.04; 95% CI, 1.02-1.06) to receive a 1-year follow-up recommendation; and patients with adenocarcinoma findings more likely to receive a 1-year follow-up recommendation compared to those with no adenocarcinoma (aOR, 10.43; 95% CI, 7.77-13.98). In addition, they found patients residing in the Northeast and those whose procedure was performed by an endoscopist with an adenoma detection rate of at least25% were more likely to receive recommendations for a repeat colonoscopy within 1 year.

“The recommendation for repeat screening or surveillance colonoscopy within 1 year when the index colonoscopy has an inadequate bowel preparation is currently a quality measure in gastroenterology,” the researchers noted. “Although our study period started in 2011, when we looked at the time period of 2014 to 2018, which is after publication of guidelines of when to repeat colonoscopy after inadequate bowel preparation, there were still low rates of guideline-concordant recommendations.”

These overall low rates, which are consistent with other studies, may be due uncertainty on the part of the endoscopist in determining inadequate bowel prep based on evolving guidelines, the researchers noted. However, the higher frequency of recommendations for repeat procedures within 1 year for patients with advanced disease suggests that endoscopists are taking pathology into account.

The study findings were limited by several factors, including the lack of standardized assessment of bowel prep quality, variation in descriptions of bowel cleanliness, and lack of information on the primary factor in follow-up recommendations. However, the results were strengthened by the large sample size, the inclusion of multiple sites and providers, and the low volume of timely repeat procedures, which has clinical implications in terms of missed lesions, “including potential interval CRC [colorectal cancer],” the researchers said.
 

Get the word out on describing preps and planning follow-ups

The current study is important because it highlights that, even when endoscopists have a reasonable understanding on how to set follow-up intervals for polyp follow-up, what to do with a patient who comes in poorly prepped is more of a problem, Kim L. Isaacs, MD, of the University of North Carolina at Chapel Hill, said in an interview.

Dr Isaacs said she was not surprised by the study findings. “There are all gradations of inadequate preps that limit visualization in different ways, and there are many ways of recording this on procedure reports. The findings in the current study emphasize several points. The first is that the recommendation of following up an inadequate or poor prep in a year needs to be widely disseminated. The second is that there needs to be more education on standardization on how preps are described. In some poor preps, much of the colon can be seen, and clinicians can identify polyps 5-6 mm, so a 1-year follow-up may not be needed.” This type of research is challenging if the data are not standardized, she added. 

Dr. Isaacs agreed with the authors’ description of repeat colonoscopies after poor bowel prep as a quality improvement area given the variability in following current recommendations, which leads into next steps for research.

“Understanding reasons for the recommendations that endoscopists made for follow-up would be the next step in this type of research,” Dr Isaacs noted. “After that, studies on the impact of an educational intervention, followed by repeating the initial assessment.”

The study received no outside funding. The researchers had no financial conflicts to disclose; however, lead author Dr. Calderwood disclosed support from the National Cancer Institute, the Dartmouth-Hitchcock Cancer Research Fellows Program, the Dartmouth-Hitchcock Norris Cotton Cancer Center, and the Dartmouth Clinical and Translational Science Institute. Dr Isaacs had no financial conflicts to disclose but has previously served on the editorial board of GI & Hepatology News.

Approximately one-third of colonoscopies with inadequate bowel preparation were repeated within 1 year despite current guidelines, according to data from a new study of more than 260,000 procedures.

Eraxion/Thinkstock

Previous studies have shown that poor bowel prep, which occurs in approximately 25% of colonoscopies, can lead to lesion miss rates of as much as 42%-48%, Audrey H. Calderwood, MD, an associate professor of medicine at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and colleagues wrote. However, factors affecting recommendations for repeat colonoscopies following poor bowel prep have not been examined.

In the study, published in Gastrointestinal Endoscopy, the researchers conducted a cross-sectional retrospective analysis of 260,314 colonoscopies reported to the GI Quality Improvement Consortium (GIQuIC) from 2011 to 2018. The review included adults aged 50-75 years in whom bowel preparation was deemed inadequate. The GIQuIC database defines adequate bowel preparation as “sufficient to accurately detect polyps greater than 5 mm in size,” the researchers noted. The procedures in this study were performed at 672 sites by 4,001 endoscopists, and the primary outcome was a recommendation for a repeat colonoscopy within 1 year.

In 31.9% of the procedures, the recommended follow-up interval for repeat colonoscopy was within 1 year, and there were no significant differences according to indication for the procedures (32.3% of screening and 31.2% of surveillance). Of these, 54.9% of patients received a follow-up interval of 1 year and 24.7% a follow-up interval within 3 months. Only 2.4% were advised they required no follow-up procedure.

The researchers found that patients with more severe disease had a higher likelihood of receiving a recommendation for follow-up colonoscopy within 1 year – 84% with adenocarcinoma, 51.8% with advanced lesions, and 23.2% with one to two small adenomas.

In the multivariate analysis, there were specific patient factors significantly associated with 1-year follow-up recommendations. The researchers found patients aged 70-75 years were less likely than younger patients (adjusted odds ratio, 0.96; 95% confidence interval, 0.93-0.98) to receive a 1-year follow-up recommendation; men were more likely than women (aOR, 1.04; 95% CI, 1.02-1.06) to receive a 1-year follow-up recommendation; and patients with adenocarcinoma findings more likely to receive a 1-year follow-up recommendation compared to those with no adenocarcinoma (aOR, 10.43; 95% CI, 7.77-13.98). In addition, they found patients residing in the Northeast and those whose procedure was performed by an endoscopist with an adenoma detection rate of at least25% were more likely to receive recommendations for a repeat colonoscopy within 1 year.

“The recommendation for repeat screening or surveillance colonoscopy within 1 year when the index colonoscopy has an inadequate bowel preparation is currently a quality measure in gastroenterology,” the researchers noted. “Although our study period started in 2011, when we looked at the time period of 2014 to 2018, which is after publication of guidelines of when to repeat colonoscopy after inadequate bowel preparation, there were still low rates of guideline-concordant recommendations.”

These overall low rates, which are consistent with other studies, may be due uncertainty on the part of the endoscopist in determining inadequate bowel prep based on evolving guidelines, the researchers noted. However, the higher frequency of recommendations for repeat procedures within 1 year for patients with advanced disease suggests that endoscopists are taking pathology into account.

The study findings were limited by several factors, including the lack of standardized assessment of bowel prep quality, variation in descriptions of bowel cleanliness, and lack of information on the primary factor in follow-up recommendations. However, the results were strengthened by the large sample size, the inclusion of multiple sites and providers, and the low volume of timely repeat procedures, which has clinical implications in terms of missed lesions, “including potential interval CRC [colorectal cancer],” the researchers said.
 

Get the word out on describing preps and planning follow-ups

The current study is important because it highlights that, even when endoscopists have a reasonable understanding on how to set follow-up intervals for polyp follow-up, what to do with a patient who comes in poorly prepped is more of a problem, Kim L. Isaacs, MD, of the University of North Carolina at Chapel Hill, said in an interview.

Dr Isaacs said she was not surprised by the study findings. “There are all gradations of inadequate preps that limit visualization in different ways, and there are many ways of recording this on procedure reports. The findings in the current study emphasize several points. The first is that the recommendation of following up an inadequate or poor prep in a year needs to be widely disseminated. The second is that there needs to be more education on standardization on how preps are described. In some poor preps, much of the colon can be seen, and clinicians can identify polyps 5-6 mm, so a 1-year follow-up may not be needed.” This type of research is challenging if the data are not standardized, she added. 

Dr. Isaacs agreed with the authors’ description of repeat colonoscopies after poor bowel prep as a quality improvement area given the variability in following current recommendations, which leads into next steps for research.

“Understanding reasons for the recommendations that endoscopists made for follow-up would be the next step in this type of research,” Dr Isaacs noted. “After that, studies on the impact of an educational intervention, followed by repeating the initial assessment.”

The study received no outside funding. The researchers had no financial conflicts to disclose; however, lead author Dr. Calderwood disclosed support from the National Cancer Institute, the Dartmouth-Hitchcock Cancer Research Fellows Program, the Dartmouth-Hitchcock Norris Cotton Cancer Center, and the Dartmouth Clinical and Translational Science Institute. Dr Isaacs had no financial conflicts to disclose but has previously served on the editorial board of GI & Hepatology News.

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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