Susan London

SAN FRANCISCO – The combination of cisplatin and gemcitabine is highly efficacious as first-line therapy for advanced pancreatic cancer in patients with a germline BRCA1/2 or PALB2 mutation, with no additional benefit seen from concurrent veliparib, a phase 2 randomized controlled trial finds.

MDedge News/Susan London

Up to 9% of pancreatic ductal adenocarcinomas occur in individuals with one of these germline mutations, which render cells more sensitive to platinum agents and PARP inhibitors because of ineffective DNA repair.

In the trial, nearly two-thirds of patients had a response to cisplatin-gemcitabine alone, according to results reported at the 2020 GI Cancers Symposium and simultaneously published (J Clin Oncol. 2020 Jan 24. doi: 10.1200/JCO.19.02931). Although almost three-quarters had a response when the investigational PARP 1/2 inhibitor veliparib was added, the difference was not statistically significant and toxicity was greater.

“Both arms were very active and substantially exceeded the prespecified thresholds,” said lead investigator Eileen Mary O’Reilly, MD, section head of Hepatopancreaticobilary & Neuroendocrine Cancers at Memorial Sloan Kettering Cancer Center in New York.

“The doublet is our recommendation for moving forward, and we believe these data define a reference regimen for germline BRCA-mutated or PALB2-mutated pancreas cancer,” she stated, noting that the PARP inhibitor olaparib (Lynparza) conferred benefit when used as maintenance therapy in the POLO trial. “I think the strategy that at the current time is best supported by the totality of the data is platinum-based therapy upfront and then sequential use of the PARP inhibitor as a maintenance approach.”

The trial was designed in 2012, before efficacy of the FOLFIRINOX regimen was well established, so an obvious question is which chemotherapy to use, Dr. O’Reilly acknowledged.

“I would say these are the only prospective randomized data we have with platinum-based therapy in germline-mutated pancreas cancer. So it comes with a high level of evidence,” she maintained. “Nonetheless, I think FOLFIRINOX is also an option. The options are good, and it probably will depend on the patient in front of you because there certainly are some lack of toxicity advantages, for the most part, to cisplatin and gemcitabine. This was a well-tolerated regimen.”
 

Implications for practice

“I wouldn’t say this is a negative study. It’s negative with respect to the veliparib question, but otherwise, it’s a very exciting study,” Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, said in an interview. “Seeing response rates of 60% and 70% in patients with metastatic pancreatic cancer is kind of unprecedented, and that’s quite remarkable.”

The reason for the lack of additional benefit from veliparib is unclear, he said. But it may be related to the specific PARP inhibitor or to the smaller sample size or very high response rate seen with chemotherapy alone, which possibly precluded detection of a significant difference.

When choosing between chemotherapy regimens, evidence favors the doublet, according to Dr. Schilsky. “FOLFIRINOX doesn’t have a 70% response rate; it may be 35%. If it was my family member, I would say, get gemcitabine-platinum if you have a BRCA mutation.”

“I think the real take-home message, quite honestly, for most oncologists is that patients with pancreatic cancer should be tested for germline BRCA mutations,” he recommended. “It can not only help inform the therapy choice, but of course, some of these cancers are going to run in families because these are germline mutations and they are going to reveal families that have a high risk of not only pancreatic cancer, but breast, ovarian, and all the other BRCA-associated cancers.”
 

Study details

The trial was conducted among 52 patients with untreated locally advanced or metastatic pancreatic ductal adenocarcinoma. Fully 94% had a BRCA mutation, while the rest had a PALB2 mutation, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

The response rate – the trial’s primary endpoint – was 65.2% with cisplatin-gemcitabine alone and 74.1% with cisplatin-gemcitabine plus veliparib (P = .55), with both arms far exceeding not only the 10% prespecified as “acceptable,” but also the 30% prespecified as “promising.” The respective disease control rates were 78.3% and 100% (P = .02).

Median progression-free survival was 9.7 months with chemotherapy alone and 10.1 months with chemotherapy plus the PARP inhibitor (P = .73). “If you reference an unselected population, that would be about 5 to 7 months,” Dr. O’Reilly noted. Median overall survival was 16.4 months and 15.5 months, respectively (P = .6). For the entire trial cohort, the 2-year overall survival rate was 30.6% and the 3-year overall survival rate was 17.8%.

“The combination came at the expense of hematologic toxicity,” Dr. O’Reilly said, with patients given veliparib having higher rates of grade 3 or 4 neutropenia (48% vs. 30%), thrombocytopenia (55% vs. 9%), and anemia (52% vs. 35%).

In an exploratory analysis among all patients receiving 4 or more months of chemotherapy and then continuing on or starting a PARP inhibitor as their next therapy, without disease progression, median overall survival was 23.4 months, very similar to what was seen in the POLO trial, she noted.

Dr. O’Reilly disclosed that she has ties with Vesselon, Polaris, and CytomX, and that her institution receives grant/research support from Celgene, Sanofi, Genentech-Roche, AstraZeneca, BMS, Silenseed, MabVax, Halozyme, and Acta Biologica. The trial was funded by the Lustgarten Foundation, the David M. Rubenstein Center for Pancreatic Cancer Research, the Reiss Family Foundation, the National Cancer Institute’s Cancer Therapy Evaluation Program, and NCI grants. Dr. Schilsky disclosed that he has no conflicts of interest.

SOURCE: O’Reilly EM et al. 2020 GI Cancers Symposium. Abstract 639.

SAN FRANCISCO – The combination of cisplatin and gemcitabine is highly efficacious as first-line therapy for advanced pancreatic cancer in patients with a germline BRCA1/2 or PALB2 mutation, with no additional benefit seen from concurrent veliparib, a phase 2 randomized controlled trial finds.

MDedge News/Susan London

Up to 9% of pancreatic ductal adenocarcinomas occur in individuals with one of these germline mutations, which render cells more sensitive to platinum agents and PARP inhibitors because of ineffective DNA repair.

In the trial, nearly two-thirds of patients had a response to cisplatin-gemcitabine alone, according to results reported at the 2020 GI Cancers Symposium and simultaneously published (J Clin Oncol. 2020 Jan 24. doi: 10.1200/JCO.19.02931). Although almost three-quarters had a response when the investigational PARP 1/2 inhibitor veliparib was added, the difference was not statistically significant and toxicity was greater.

“Both arms were very active and substantially exceeded the prespecified thresholds,” said lead investigator Eileen Mary O’Reilly, MD, section head of Hepatopancreaticobilary & Neuroendocrine Cancers at Memorial Sloan Kettering Cancer Center in New York.

“The doublet is our recommendation for moving forward, and we believe these data define a reference regimen for germline BRCA-mutated or PALB2-mutated pancreas cancer,” she stated, noting that the PARP inhibitor olaparib (Lynparza) conferred benefit when used as maintenance therapy in the POLO trial. “I think the strategy that at the current time is best supported by the totality of the data is platinum-based therapy upfront and then sequential use of the PARP inhibitor as a maintenance approach.”

The trial was designed in 2012, before efficacy of the FOLFIRINOX regimen was well established, so an obvious question is which chemotherapy to use, Dr. O’Reilly acknowledged.

“I would say these are the only prospective randomized data we have with platinum-based therapy in germline-mutated pancreas cancer. So it comes with a high level of evidence,” she maintained. “Nonetheless, I think FOLFIRINOX is also an option. The options are good, and it probably will depend on the patient in front of you because there certainly are some lack of toxicity advantages, for the most part, to cisplatin and gemcitabine. This was a well-tolerated regimen.”
 

Implications for practice

“I wouldn’t say this is a negative study. It’s negative with respect to the veliparib question, but otherwise, it’s a very exciting study,” Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, said in an interview. “Seeing response rates of 60% and 70% in patients with metastatic pancreatic cancer is kind of unprecedented, and that’s quite remarkable.”

The reason for the lack of additional benefit from veliparib is unclear, he said. But it may be related to the specific PARP inhibitor or to the smaller sample size or very high response rate seen with chemotherapy alone, which possibly precluded detection of a significant difference.

When choosing between chemotherapy regimens, evidence favors the doublet, according to Dr. Schilsky. “FOLFIRINOX doesn’t have a 70% response rate; it may be 35%. If it was my family member, I would say, get gemcitabine-platinum if you have a BRCA mutation.”

“I think the real take-home message, quite honestly, for most oncologists is that patients with pancreatic cancer should be tested for germline BRCA mutations,” he recommended. “It can not only help inform the therapy choice, but of course, some of these cancers are going to run in families because these are germline mutations and they are going to reveal families that have a high risk of not only pancreatic cancer, but breast, ovarian, and all the other BRCA-associated cancers.”
 

Study details

The trial was conducted among 52 patients with untreated locally advanced or metastatic pancreatic ductal adenocarcinoma. Fully 94% had a BRCA mutation, while the rest had a PALB2 mutation, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

The response rate – the trial’s primary endpoint – was 65.2% with cisplatin-gemcitabine alone and 74.1% with cisplatin-gemcitabine plus veliparib (P = .55), with both arms far exceeding not only the 10% prespecified as “acceptable,” but also the 30% prespecified as “promising.” The respective disease control rates were 78.3% and 100% (P = .02).

Median progression-free survival was 9.7 months with chemotherapy alone and 10.1 months with chemotherapy plus the PARP inhibitor (P = .73). “If you reference an unselected population, that would be about 5 to 7 months,” Dr. O’Reilly noted. Median overall survival was 16.4 months and 15.5 months, respectively (P = .6). For the entire trial cohort, the 2-year overall survival rate was 30.6% and the 3-year overall survival rate was 17.8%.

“The combination came at the expense of hematologic toxicity,” Dr. O’Reilly said, with patients given veliparib having higher rates of grade 3 or 4 neutropenia (48% vs. 30%), thrombocytopenia (55% vs. 9%), and anemia (52% vs. 35%).

In an exploratory analysis among all patients receiving 4 or more months of chemotherapy and then continuing on or starting a PARP inhibitor as their next therapy, without disease progression, median overall survival was 23.4 months, very similar to what was seen in the POLO trial, she noted.

Dr. O’Reilly disclosed that she has ties with Vesselon, Polaris, and CytomX, and that her institution receives grant/research support from Celgene, Sanofi, Genentech-Roche, AstraZeneca, BMS, Silenseed, MabVax, Halozyme, and Acta Biologica. The trial was funded by the Lustgarten Foundation, the David M. Rubenstein Center for Pancreatic Cancer Research, the Reiss Family Foundation, the National Cancer Institute’s Cancer Therapy Evaluation Program, and NCI grants. Dr. Schilsky disclosed that he has no conflicts of interest.

SOURCE: O’Reilly EM et al. 2020 GI Cancers Symposium. Abstract 639.

SAN FRANCISCO – The combination of cisplatin and gemcitabine is highly efficacious as first-line therapy for advanced pancreatic cancer in patients with a germline BRCA1/2 or PALB2 mutation, with no additional benefit seen from concurrent veliparib, a phase 2 randomized controlled trial finds.

MDedge News/Susan London

Up to 9% of pancreatic ductal adenocarcinomas occur in individuals with one of these germline mutations, which render cells more sensitive to platinum agents and PARP inhibitors because of ineffective DNA repair.

In the trial, nearly two-thirds of patients had a response to cisplatin-gemcitabine alone, according to results reported at the 2020 GI Cancers Symposium and simultaneously published (J Clin Oncol. 2020 Jan 24. doi: 10.1200/JCO.19.02931). Although almost three-quarters had a response when the investigational PARP 1/2 inhibitor veliparib was added, the difference was not statistically significant and toxicity was greater.

“Both arms were very active and substantially exceeded the prespecified thresholds,” said lead investigator Eileen Mary O’Reilly, MD, section head of Hepatopancreaticobilary & Neuroendocrine Cancers at Memorial Sloan Kettering Cancer Center in New York.

“The doublet is our recommendation for moving forward, and we believe these data define a reference regimen for germline BRCA-mutated or PALB2-mutated pancreas cancer,” she stated, noting that the PARP inhibitor olaparib (Lynparza) conferred benefit when used as maintenance therapy in the POLO trial. “I think the strategy that at the current time is best supported by the totality of the data is platinum-based therapy upfront and then sequential use of the PARP inhibitor as a maintenance approach.”

The trial was designed in 2012, before efficacy of the FOLFIRINOX regimen was well established, so an obvious question is which chemotherapy to use, Dr. O’Reilly acknowledged.

“I would say these are the only prospective randomized data we have with platinum-based therapy in germline-mutated pancreas cancer. So it comes with a high level of evidence,” she maintained. “Nonetheless, I think FOLFIRINOX is also an option. The options are good, and it probably will depend on the patient in front of you because there certainly are some lack of toxicity advantages, for the most part, to cisplatin and gemcitabine. This was a well-tolerated regimen.”
 

Implications for practice

“I wouldn’t say this is a negative study. It’s negative with respect to the veliparib question, but otherwise, it’s a very exciting study,” Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, said in an interview. “Seeing response rates of 60% and 70% in patients with metastatic pancreatic cancer is kind of unprecedented, and that’s quite remarkable.”

The reason for the lack of additional benefit from veliparib is unclear, he said. But it may be related to the specific PARP inhibitor or to the smaller sample size or very high response rate seen with chemotherapy alone, which possibly precluded detection of a significant difference.

When choosing between chemotherapy regimens, evidence favors the doublet, according to Dr. Schilsky. “FOLFIRINOX doesn’t have a 70% response rate; it may be 35%. If it was my family member, I would say, get gemcitabine-platinum if you have a BRCA mutation.”

“I think the real take-home message, quite honestly, for most oncologists is that patients with pancreatic cancer should be tested for germline BRCA mutations,” he recommended. “It can not only help inform the therapy choice, but of course, some of these cancers are going to run in families because these are germline mutations and they are going to reveal families that have a high risk of not only pancreatic cancer, but breast, ovarian, and all the other BRCA-associated cancers.”
 

Study details

The trial was conducted among 52 patients with untreated locally advanced or metastatic pancreatic ductal adenocarcinoma. Fully 94% had a BRCA mutation, while the rest had a PALB2 mutation, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

The response rate – the trial’s primary endpoint – was 65.2% with cisplatin-gemcitabine alone and 74.1% with cisplatin-gemcitabine plus veliparib (P = .55), with both arms far exceeding not only the 10% prespecified as “acceptable,” but also the 30% prespecified as “promising.” The respective disease control rates were 78.3% and 100% (P = .02).

Median progression-free survival was 9.7 months with chemotherapy alone and 10.1 months with chemotherapy plus the PARP inhibitor (P = .73). “If you reference an unselected population, that would be about 5 to 7 months,” Dr. O’Reilly noted. Median overall survival was 16.4 months and 15.5 months, respectively (P = .6). For the entire trial cohort, the 2-year overall survival rate was 30.6% and the 3-year overall survival rate was 17.8%.

“The combination came at the expense of hematologic toxicity,” Dr. O’Reilly said, with patients given veliparib having higher rates of grade 3 or 4 neutropenia (48% vs. 30%), thrombocytopenia (55% vs. 9%), and anemia (52% vs. 35%).

In an exploratory analysis among all patients receiving 4 or more months of chemotherapy and then continuing on or starting a PARP inhibitor as their next therapy, without disease progression, median overall survival was 23.4 months, very similar to what was seen in the POLO trial, she noted.

Dr. O’Reilly disclosed that she has ties with Vesselon, Polaris, and CytomX, and that her institution receives grant/research support from Celgene, Sanofi, Genentech-Roche, AstraZeneca, BMS, Silenseed, MabVax, Halozyme, and Acta Biologica. The trial was funded by the Lustgarten Foundation, the David M. Rubenstein Center for Pancreatic Cancer Research, the Reiss Family Foundation, the National Cancer Institute’s Cancer Therapy Evaluation Program, and NCI grants. Dr. Schilsky disclosed that he has no conflicts of interest.

SOURCE: O’Reilly EM et al. 2020 GI Cancers Symposium. Abstract 639.

SAN FRANCISCO – Young adults with colorectal cancer who live in neighborhoods with higher levels of disadvantage differ on health measures, present with more advanced disease, and have poorer survival. These were among key findings of a retrospective cohort study reported at the 2020 GI Cancers Symposium.

MDedge/Susan London

The incidence of colorectal cancer has risen sharply – 51% – since 1994 among individuals aged younger than age 50 years, with the greatest uptick seen among those aged 20-29 years (J Natl Cancer Inst. 2017;109[8]. doi: 10.1093/jnci/djw322).

“Sociodemographic disparities have been linked to inferior survival. However, their impact and association with outcome in young adults is not well described,” said lead investigator Ashley Matusz-Fisher, MD, of the Levine Cancer Institute in Charlotte, N.C.

The investigators analyzed data from the National Cancer Database for the years 2004-2016, identifying 26,768 patients who received a colorectal cancer diagnosis when aged 18-40 years.

Results showed that those living in areas with low income (less than $38,000 annually) and low educational attainment (high school graduation rate less than 79%), and those living in urban or rural areas (versus metropolitan areas) had 24% and 10% higher risks of death, respectively.

Patients in the low-income, low-education group were more than six times as likely to be black and to lack private health insurance, had greater comorbidity, had larger tumors and more nodal involvement at diagnosis, and were less likely to undergo surgery.

Several factors may be at play for the low-income, low-education group, Dr. Matusz-Fisher speculated: limited access to care, lack of awareness of important symptoms, and inability to afford treatment when it is needed. “That could very well be contributing to them presenting at later stages and then maybe not getting the treatment that other people who have insurance would be getting.

“To try to eliminate these disparities, the first step is recognition, which is what we are doing – recognizing there are disparities – and then making people aware of these disparities,” she commented. “More efforts are needed to increase access and remove barriers to care, with the hope of eliminating disparities and achieving health equity.”

Mitigating disparities

Several studies have looked at mitigating sociodemographic-related disparities in colorectal cancer outcomes, according to session cochair John M. Carethers, MD, AGAF, professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.

MDedge/Susan London

A large Delaware initiative tackled the problem via screening (J Clin Oncol. 2013;31:1928-30). “Now this was over 50 – we don’t typically screen under 50 – but over 50, you can essentially eliminate this disparity with navigation services and screening. How do you do that under 50? I’m not quite sure,” he said in an interview, adding that some organizations are recommending lowering the screening age to 45 or even 40 years in light of rising incidence among young adults.

However, accumulating evidence suggests that there may be inherent biological differences that are harder to overcome. “There is a lot of data … showing that polyps happen earlier and they are bigger in certain racial groups, particularly African Americans and American Indians,” Dr. Carethers elaborated. What is driving the biology is unknown, but the microbiome has come under scrutiny.

“So you are a victim of your circumstances,” he summarized. “You are living in a low-income area, you are eating more proinflammatory-type foods, you are getting your polyps earlier, and then you are getting your cancers earlier.”

Study details

Rural, urban, or metropolitan status was ascertained for 25,861 patients in the study, and area income and education were ascertained for 7,743 patients, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Compared with counterparts living in areas with both high annual income (greater than $68,000) and education (greater than 93% high school graduation rate), patients living in areas with both low annual income (less than $38,000) and education ( less than 79% high school graduation rate) were significantly more likely to be black (odds ratio, 6.4), not have private insurance (odds ratio, 6.3), have pathologic T3/T4 stage (OR, 1.4), have positive nodes (OR, 1.2), and have a Charlson-Deyo comorbidity score of 1 or greater (OR, 1.6). They also were less likely to undergo surgery (OR, 0.63) and more likely to be rehospitalized within 30 days (OR, 1.3).

After adjusting for race, insurance status, T/N stage, and comorbidity score, relative to counterparts in the high-income, high-education group, patients in the low-income, low-education group had an increased risk of death (hazard ratio, 1.24; P = .004). And relative to counterparts living in metropolitan areas, patients living in urban or rural areas had an increased risk of death (HR, 1.10; P = .02).

Among patients with stage IV disease, median overall survival was 26.1 months for those from high-income, high-education areas, but 20.7 months for those from low-income, low-education areas (P less than .001).

Dr. Matusz-Fisher did not report any conflicts of interest. The study did not receive any funding.

SOURCE: Matusz-Fisher A et al. 2020 GI Cancers Symposium, Abstract 13.

SAN FRANCISCO – Young adults with colorectal cancer who live in neighborhoods with higher levels of disadvantage differ on health measures, present with more advanced disease, and have poorer survival. These were among key findings of a retrospective cohort study reported at the 2020 GI Cancers Symposium.

MDedge/Susan London

The incidence of colorectal cancer has risen sharply – 51% – since 1994 among individuals aged younger than age 50 years, with the greatest uptick seen among those aged 20-29 years (J Natl Cancer Inst. 2017;109[8]. doi: 10.1093/jnci/djw322).

“Sociodemographic disparities have been linked to inferior survival. However, their impact and association with outcome in young adults is not well described,” said lead investigator Ashley Matusz-Fisher, MD, of the Levine Cancer Institute in Charlotte, N.C.

The investigators analyzed data from the National Cancer Database for the years 2004-2016, identifying 26,768 patients who received a colorectal cancer diagnosis when aged 18-40 years.

Results showed that those living in areas with low income (less than $38,000 annually) and low educational attainment (high school graduation rate less than 79%), and those living in urban or rural areas (versus metropolitan areas) had 24% and 10% higher risks of death, respectively.

Patients in the low-income, low-education group were more than six times as likely to be black and to lack private health insurance, had greater comorbidity, had larger tumors and more nodal involvement at diagnosis, and were less likely to undergo surgery.

Several factors may be at play for the low-income, low-education group, Dr. Matusz-Fisher speculated: limited access to care, lack of awareness of important symptoms, and inability to afford treatment when it is needed. “That could very well be contributing to them presenting at later stages and then maybe not getting the treatment that other people who have insurance would be getting.

“To try to eliminate these disparities, the first step is recognition, which is what we are doing – recognizing there are disparities – and then making people aware of these disparities,” she commented. “More efforts are needed to increase access and remove barriers to care, with the hope of eliminating disparities and achieving health equity.”

Mitigating disparities

Several studies have looked at mitigating sociodemographic-related disparities in colorectal cancer outcomes, according to session cochair John M. Carethers, MD, AGAF, professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.

MDedge/Susan London

A large Delaware initiative tackled the problem via screening (J Clin Oncol. 2013;31:1928-30). “Now this was over 50 – we don’t typically screen under 50 – but over 50, you can essentially eliminate this disparity with navigation services and screening. How do you do that under 50? I’m not quite sure,” he said in an interview, adding that some organizations are recommending lowering the screening age to 45 or even 40 years in light of rising incidence among young adults.

However, accumulating evidence suggests that there may be inherent biological differences that are harder to overcome. “There is a lot of data … showing that polyps happen earlier and they are bigger in certain racial groups, particularly African Americans and American Indians,” Dr. Carethers elaborated. What is driving the biology is unknown, but the microbiome has come under scrutiny.

“So you are a victim of your circumstances,” he summarized. “You are living in a low-income area, you are eating more proinflammatory-type foods, you are getting your polyps earlier, and then you are getting your cancers earlier.”

Study details

Rural, urban, or metropolitan status was ascertained for 25,861 patients in the study, and area income and education were ascertained for 7,743 patients, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Compared with counterparts living in areas with both high annual income (greater than $68,000) and education (greater than 93% high school graduation rate), patients living in areas with both low annual income (less than $38,000) and education ( less than 79% high school graduation rate) were significantly more likely to be black (odds ratio, 6.4), not have private insurance (odds ratio, 6.3), have pathologic T3/T4 stage (OR, 1.4), have positive nodes (OR, 1.2), and have a Charlson-Deyo comorbidity score of 1 or greater (OR, 1.6). They also were less likely to undergo surgery (OR, 0.63) and more likely to be rehospitalized within 30 days (OR, 1.3).

After adjusting for race, insurance status, T/N stage, and comorbidity score, relative to counterparts in the high-income, high-education group, patients in the low-income, low-education group had an increased risk of death (hazard ratio, 1.24; P = .004). And relative to counterparts living in metropolitan areas, patients living in urban or rural areas had an increased risk of death (HR, 1.10; P = .02).

Among patients with stage IV disease, median overall survival was 26.1 months for those from high-income, high-education areas, but 20.7 months for those from low-income, low-education areas (P less than .001).

Dr. Matusz-Fisher did not report any conflicts of interest. The study did not receive any funding.

SOURCE: Matusz-Fisher A et al. 2020 GI Cancers Symposium, Abstract 13.

SAN FRANCISCO – Young adults with colorectal cancer who live in neighborhoods with higher levels of disadvantage differ on health measures, present with more advanced disease, and have poorer survival. These were among key findings of a retrospective cohort study reported at the 2020 GI Cancers Symposium.

MDedge/Susan London

The incidence of colorectal cancer has risen sharply – 51% – since 1994 among individuals aged younger than age 50 years, with the greatest uptick seen among those aged 20-29 years (J Natl Cancer Inst. 2017;109[8]. doi: 10.1093/jnci/djw322).

“Sociodemographic disparities have been linked to inferior survival. However, their impact and association with outcome in young adults is not well described,” said lead investigator Ashley Matusz-Fisher, MD, of the Levine Cancer Institute in Charlotte, N.C.

The investigators analyzed data from the National Cancer Database for the years 2004-2016, identifying 26,768 patients who received a colorectal cancer diagnosis when aged 18-40 years.

Results showed that those living in areas with low income (less than $38,000 annually) and low educational attainment (high school graduation rate less than 79%), and those living in urban or rural areas (versus metropolitan areas) had 24% and 10% higher risks of death, respectively.

Patients in the low-income, low-education group were more than six times as likely to be black and to lack private health insurance, had greater comorbidity, had larger tumors and more nodal involvement at diagnosis, and were less likely to undergo surgery.

Several factors may be at play for the low-income, low-education group, Dr. Matusz-Fisher speculated: limited access to care, lack of awareness of important symptoms, and inability to afford treatment when it is needed. “That could very well be contributing to them presenting at later stages and then maybe not getting the treatment that other people who have insurance would be getting.

“To try to eliminate these disparities, the first step is recognition, which is what we are doing – recognizing there are disparities – and then making people aware of these disparities,” she commented. “More efforts are needed to increase access and remove barriers to care, with the hope of eliminating disparities and achieving health equity.”

Mitigating disparities

Several studies have looked at mitigating sociodemographic-related disparities in colorectal cancer outcomes, according to session cochair John M. Carethers, MD, AGAF, professor and chair of the department of internal medicine at the University of Michigan, Ann Arbor.

MDedge/Susan London

A large Delaware initiative tackled the problem via screening (J Clin Oncol. 2013;31:1928-30). “Now this was over 50 – we don’t typically screen under 50 – but over 50, you can essentially eliminate this disparity with navigation services and screening. How do you do that under 50? I’m not quite sure,” he said in an interview, adding that some organizations are recommending lowering the screening age to 45 or even 40 years in light of rising incidence among young adults.

However, accumulating evidence suggests that there may be inherent biological differences that are harder to overcome. “There is a lot of data … showing that polyps happen earlier and they are bigger in certain racial groups, particularly African Americans and American Indians,” Dr. Carethers elaborated. What is driving the biology is unknown, but the microbiome has come under scrutiny.

“So you are a victim of your circumstances,” he summarized. “You are living in a low-income area, you are eating more proinflammatory-type foods, you are getting your polyps earlier, and then you are getting your cancers earlier.”

Study details

Rural, urban, or metropolitan status was ascertained for 25,861 patients in the study, and area income and education were ascertained for 7,743 patients, according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Compared with counterparts living in areas with both high annual income (greater than $68,000) and education (greater than 93% high school graduation rate), patients living in areas with both low annual income (less than $38,000) and education ( less than 79% high school graduation rate) were significantly more likely to be black (odds ratio, 6.4), not have private insurance (odds ratio, 6.3), have pathologic T3/T4 stage (OR, 1.4), have positive nodes (OR, 1.2), and have a Charlson-Deyo comorbidity score of 1 or greater (OR, 1.6). They also were less likely to undergo surgery (OR, 0.63) and more likely to be rehospitalized within 30 days (OR, 1.3).

After adjusting for race, insurance status, T/N stage, and comorbidity score, relative to counterparts in the high-income, high-education group, patients in the low-income, low-education group had an increased risk of death (hazard ratio, 1.24; P = .004). And relative to counterparts living in metropolitan areas, patients living in urban or rural areas had an increased risk of death (HR, 1.10; P = .02).

Among patients with stage IV disease, median overall survival was 26.1 months for those from high-income, high-education areas, but 20.7 months for those from low-income, low-education areas (P less than .001).

Dr. Matusz-Fisher did not report any conflicts of interest. The study did not receive any funding.

SOURCE: Matusz-Fisher A et al. 2020 GI Cancers Symposium, Abstract 13.

SAN FRANCISCO – A new assay based on methylation patterns in plasma cell-free DNA holds promise for improving detection of diverse gastrointestinal (GI) cancers when they are still curable, findings of the Circulating Cell-free Genome Atlas (CCGA) study suggest.

Susan London/MDedge News

Among 447 patients with GI cancers of varied types and stages, the multicancer assay had sensitivity exceeding 80% for all stages (exceeding 70% for stages I to III) and specificity exceeding 99%, investigators reported at the 2020 GI Cancers Symposium. In addition, the assay correctly determined the tissue of origin about 90% of the time.

“To pursue early detection at a population scale while minimizing harm and cost, several features are important, including a low false-positive rate, a high detection rate, the ability to localize the site of origin of the malignancy, and limiting overdiagnosis,” noted lead investigator Brian M. Wolpin, MD, MPH, director of the Gastrointestinal Cancer Center and director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston. “This multicancer early detection test evaluating cell-free DNA methylation may be a useful test to detect GI cancers and may guide further evaluation and workup.”

About three-quarters of all cancer patients in the study had symptoms that ultimately led to their diagnosis, Dr. Wolpin acknowledged. But the investigators are conducting two large additional studies among asymptomatic populations to better assess the assay’s screening potential: the STRIVE study, which has enrolled nearly 100,000 women undergoing screening mammography, and the SUMMIT study, which is enrolling 50,000 men and women without a known cancer diagnosis, with enrichment of the sample for smokers.
 

Clinical potential

“The holy grail, of course, is to try to find any test – a blood test, a urine test, a breath test, a stool test – that will allow us to detect cancer at an earlier and more curable stage, and we have hints now that we are headed in the right direction,” session cochair George A. Fisher Jr., MD, PhD, said in an interview. “I don’t know that this is the technology that will do it, but I think it’s superior to the technology just looking at DNA mutations.”

Susan London/MDedge News

It is a further merit that the assay also has good accuracy in ascertaining the cancer’s tissue of origin, as that should help streamline the diagnostic workup, he agreed.

The assay is already attractive for patients with suspicious lesions or symptoms, but further research will be needed to assess its performance in detecting asymptomatic cancer, and logistic issues would have to be addressed, according to Dr. Fisher of Stanford (Calif.) University.

“As an outright screening test, I don’t think we are there yet. We would have to identify the populations in whom to use the test and come up with some frequency of how often we use it,” he said. Consideration would need to be given to informed consent, especially as some patients may have a positive assay result but a cancer that can’t be found, generating psychological distress.

And cost will come into play. “The problem is, for most stage I cancers you can screen for, they are still very low in likelihood, so you have to screen a lot of people, which means a lot of expense,” he elaborated.

“It will be interesting in the research world to decide when such a test would become a reasonable standard of care, and how regulators will view that and how insurers will view that in terms of cost-efficacy analysis,” Dr. Fisher concluded.
 

Study details

The CCGA study has enrolled 15,254 participants with and without cancer at 142 U.S and Canadian sites. Participants provide blood samples (at diagnosis for those with cancer) and are followed up for 5 years.

To develop the assay, the investigators performed targeted methylation sequencing of cell-free DNA from plasma and trained an algorithm to use the methylation patterns to detect more than 20 cancer types and classify them based on the organ of origin.

Dr. Wolpin reported results for a CCGA substudy conducted among 2,185 patients with cancer and 2,131 individuals without cancer. About a fifth of the former group had cancers of the GI tract (colon or rectum in 174 patients, pancreas in 123, esophagus in 71, liver or bile duct in 40, stomach in 25, gallbladder in 14). The population was split into training and validation sets.

The assay had a specificity of 99.8% in the entire training set and 99.3% in the entire validation set, corresponding to false-positives in just 0.2% and 0.7% of the individuals without cancer, according to data reported at the symposium, which is sponsored by the American Gastroenterological Association, American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

For GI cancers, assay sensitivity for stage I-IV disease was 82% in the training set and 81% in the validation set, and sensitivity for stage I-III disease was 73% and 71%, respectively. By specific nonmetastatic stage, sensitivity was about 50% for stage I disease, 75% for stage II disease, and 85% for stage III disease.

Fully 97% of the GI cancers having detectable cell-free DNA were assigned a tissue of origin by the assay. The predicted tissue of origin had an accuracy of 91% in the training set and 89% in the validation set, with similar values across GI cancer types.

Dr. Wolpin disclosed having a relationship with various pharmaceutical companies, including GRAIL, which funded the study. Dr. Fisher disclosed relationships with numerous pharmaceutical companies and that an immediate family member has stock in Seattle Genetics

SOURCE: Wolpin BM et al. 2020 GI Symposium, Abstract 283.

SAN FRANCISCO – A new assay based on methylation patterns in plasma cell-free DNA holds promise for improving detection of diverse gastrointestinal (GI) cancers when they are still curable, findings of the Circulating Cell-free Genome Atlas (CCGA) study suggest.

Susan London/MDedge News

Among 447 patients with GI cancers of varied types and stages, the multicancer assay had sensitivity exceeding 80% for all stages (exceeding 70% for stages I to III) and specificity exceeding 99%, investigators reported at the 2020 GI Cancers Symposium. In addition, the assay correctly determined the tissue of origin about 90% of the time.

“To pursue early detection at a population scale while minimizing harm and cost, several features are important, including a low false-positive rate, a high detection rate, the ability to localize the site of origin of the malignancy, and limiting overdiagnosis,” noted lead investigator Brian M. Wolpin, MD, MPH, director of the Gastrointestinal Cancer Center and director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston. “This multicancer early detection test evaluating cell-free DNA methylation may be a useful test to detect GI cancers and may guide further evaluation and workup.”

About three-quarters of all cancer patients in the study had symptoms that ultimately led to their diagnosis, Dr. Wolpin acknowledged. But the investigators are conducting two large additional studies among asymptomatic populations to better assess the assay’s screening potential: the STRIVE study, which has enrolled nearly 100,000 women undergoing screening mammography, and the SUMMIT study, which is enrolling 50,000 men and women without a known cancer diagnosis, with enrichment of the sample for smokers.
 

Clinical potential

“The holy grail, of course, is to try to find any test – a blood test, a urine test, a breath test, a stool test – that will allow us to detect cancer at an earlier and more curable stage, and we have hints now that we are headed in the right direction,” session cochair George A. Fisher Jr., MD, PhD, said in an interview. “I don’t know that this is the technology that will do it, but I think it’s superior to the technology just looking at DNA mutations.”

Susan London/MDedge News

It is a further merit that the assay also has good accuracy in ascertaining the cancer’s tissue of origin, as that should help streamline the diagnostic workup, he agreed.

The assay is already attractive for patients with suspicious lesions or symptoms, but further research will be needed to assess its performance in detecting asymptomatic cancer, and logistic issues would have to be addressed, according to Dr. Fisher of Stanford (Calif.) University.

“As an outright screening test, I don’t think we are there yet. We would have to identify the populations in whom to use the test and come up with some frequency of how often we use it,” he said. Consideration would need to be given to informed consent, especially as some patients may have a positive assay result but a cancer that can’t be found, generating psychological distress.

And cost will come into play. “The problem is, for most stage I cancers you can screen for, they are still very low in likelihood, so you have to screen a lot of people, which means a lot of expense,” he elaborated.

“It will be interesting in the research world to decide when such a test would become a reasonable standard of care, and how regulators will view that and how insurers will view that in terms of cost-efficacy analysis,” Dr. Fisher concluded.
 

Study details

The CCGA study has enrolled 15,254 participants with and without cancer at 142 U.S and Canadian sites. Participants provide blood samples (at diagnosis for those with cancer) and are followed up for 5 years.

To develop the assay, the investigators performed targeted methylation sequencing of cell-free DNA from plasma and trained an algorithm to use the methylation patterns to detect more than 20 cancer types and classify them based on the organ of origin.

Dr. Wolpin reported results for a CCGA substudy conducted among 2,185 patients with cancer and 2,131 individuals without cancer. About a fifth of the former group had cancers of the GI tract (colon or rectum in 174 patients, pancreas in 123, esophagus in 71, liver or bile duct in 40, stomach in 25, gallbladder in 14). The population was split into training and validation sets.

The assay had a specificity of 99.8% in the entire training set and 99.3% in the entire validation set, corresponding to false-positives in just 0.2% and 0.7% of the individuals without cancer, according to data reported at the symposium, which is sponsored by the American Gastroenterological Association, American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

For GI cancers, assay sensitivity for stage I-IV disease was 82% in the training set and 81% in the validation set, and sensitivity for stage I-III disease was 73% and 71%, respectively. By specific nonmetastatic stage, sensitivity was about 50% for stage I disease, 75% for stage II disease, and 85% for stage III disease.

Fully 97% of the GI cancers having detectable cell-free DNA were assigned a tissue of origin by the assay. The predicted tissue of origin had an accuracy of 91% in the training set and 89% in the validation set, with similar values across GI cancer types.

Dr. Wolpin disclosed having a relationship with various pharmaceutical companies, including GRAIL, which funded the study. Dr. Fisher disclosed relationships with numerous pharmaceutical companies and that an immediate family member has stock in Seattle Genetics

SOURCE: Wolpin BM et al. 2020 GI Symposium, Abstract 283.

SAN FRANCISCO – A new assay based on methylation patterns in plasma cell-free DNA holds promise for improving detection of diverse gastrointestinal (GI) cancers when they are still curable, findings of the Circulating Cell-free Genome Atlas (CCGA) study suggest.

Susan London/MDedge News

Among 447 patients with GI cancers of varied types and stages, the multicancer assay had sensitivity exceeding 80% for all stages (exceeding 70% for stages I to III) and specificity exceeding 99%, investigators reported at the 2020 GI Cancers Symposium. In addition, the assay correctly determined the tissue of origin about 90% of the time.

“To pursue early detection at a population scale while minimizing harm and cost, several features are important, including a low false-positive rate, a high detection rate, the ability to localize the site of origin of the malignancy, and limiting overdiagnosis,” noted lead investigator Brian M. Wolpin, MD, MPH, director of the Gastrointestinal Cancer Center and director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston. “This multicancer early detection test evaluating cell-free DNA methylation may be a useful test to detect GI cancers and may guide further evaluation and workup.”

About three-quarters of all cancer patients in the study had symptoms that ultimately led to their diagnosis, Dr. Wolpin acknowledged. But the investigators are conducting two large additional studies among asymptomatic populations to better assess the assay’s screening potential: the STRIVE study, which has enrolled nearly 100,000 women undergoing screening mammography, and the SUMMIT study, which is enrolling 50,000 men and women without a known cancer diagnosis, with enrichment of the sample for smokers.
 

Clinical potential

“The holy grail, of course, is to try to find any test – a blood test, a urine test, a breath test, a stool test – that will allow us to detect cancer at an earlier and more curable stage, and we have hints now that we are headed in the right direction,” session cochair George A. Fisher Jr., MD, PhD, said in an interview. “I don’t know that this is the technology that will do it, but I think it’s superior to the technology just looking at DNA mutations.”

Susan London/MDedge News

It is a further merit that the assay also has good accuracy in ascertaining the cancer’s tissue of origin, as that should help streamline the diagnostic workup, he agreed.

The assay is already attractive for patients with suspicious lesions or symptoms, but further research will be needed to assess its performance in detecting asymptomatic cancer, and logistic issues would have to be addressed, according to Dr. Fisher of Stanford (Calif.) University.

“As an outright screening test, I don’t think we are there yet. We would have to identify the populations in whom to use the test and come up with some frequency of how often we use it,” he said. Consideration would need to be given to informed consent, especially as some patients may have a positive assay result but a cancer that can’t be found, generating psychological distress.

And cost will come into play. “The problem is, for most stage I cancers you can screen for, they are still very low in likelihood, so you have to screen a lot of people, which means a lot of expense,” he elaborated.

“It will be interesting in the research world to decide when such a test would become a reasonable standard of care, and how regulators will view that and how insurers will view that in terms of cost-efficacy analysis,” Dr. Fisher concluded.
 

Study details

The CCGA study has enrolled 15,254 participants with and without cancer at 142 U.S and Canadian sites. Participants provide blood samples (at diagnosis for those with cancer) and are followed up for 5 years.

To develop the assay, the investigators performed targeted methylation sequencing of cell-free DNA from plasma and trained an algorithm to use the methylation patterns to detect more than 20 cancer types and classify them based on the organ of origin.

Dr. Wolpin reported results for a CCGA substudy conducted among 2,185 patients with cancer and 2,131 individuals without cancer. About a fifth of the former group had cancers of the GI tract (colon or rectum in 174 patients, pancreas in 123, esophagus in 71, liver or bile duct in 40, stomach in 25, gallbladder in 14). The population was split into training and validation sets.

The assay had a specificity of 99.8% in the entire training set and 99.3% in the entire validation set, corresponding to false-positives in just 0.2% and 0.7% of the individuals without cancer, according to data reported at the symposium, which is sponsored by the American Gastroenterological Association, American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

For GI cancers, assay sensitivity for stage I-IV disease was 82% in the training set and 81% in the validation set, and sensitivity for stage I-III disease was 73% and 71%, respectively. By specific nonmetastatic stage, sensitivity was about 50% for stage I disease, 75% for stage II disease, and 85% for stage III disease.

Fully 97% of the GI cancers having detectable cell-free DNA were assigned a tissue of origin by the assay. The predicted tissue of origin had an accuracy of 91% in the training set and 89% in the validation set, with similar values across GI cancer types.

Dr. Wolpin disclosed having a relationship with various pharmaceutical companies, including GRAIL, which funded the study. Dr. Fisher disclosed relationships with numerous pharmaceutical companies and that an immediate family member has stock in Seattle Genetics

SOURCE: Wolpin BM et al. 2020 GI Symposium, Abstract 283.

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.

Patients with advanced urothelial cancer and a poor performance status may have little to gain from immune checkpoint inhibitor therapy, suggests a multicenter real-world retrospective cohort study.

“The perceived favorable toxicity profile of immune checkpoint inhibitors has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy,” noted the investigators, led by Ali Raza Khaki, MD, a fellow in the division of oncology, department of medicine, University of Washington, Seattle. “However, there is a paucity of data supporting the use of immune checkpoint inhibitors in patients with a poor performance status, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG [Eastern Cooperative Oncology Group] performance status greater than or equal to 3 and only 3 trials including patients with an ECOG performance status of 2.”

Dr. Khaki and coinvestigators analyzed data from 499 patients with advanced urothelial cancer treated with immune checkpoint inhibitors at 18 institutions during 2013-2019. Slightly more than one-quarter had an ECOG performance status of 2 or higher.

Study results, reported in Cancer, showed that the overall response rate to immune checkpoint inhibitor therapy was similar regardless of performance status, across patients being treated in different lines of therapy.

However, among patients being treated in the first line, overall survival was better for those with a performance status of 0 to 1 than for those with a performance status of 2 or higher (median, 15.2 vs. 7.2 months; hazard ratio for death, 0.62; P = .01). There was no significant difference in this outcome among patients being treated in subsequent lines (median, 9.8 vs. 8.2 months; hazard ratio, 0.78; P = .27).

Among the 288 patients who died, 10% started immune checkpoint inhibitors in the last 30 days of life and 33% started them in the last 90 days of life. Patients initiating this therapy in the last 30 days of life were almost three time more likely to die in a hospital (odds ratio, 2.89; P = .04).

SOURCE: Khaki AR et al. Cancer. 2019 Dec 12. doi: 10.1002/cncr.32645.

More is not better when it comes to radiation therapy administered with concurrent chemotherapy for unresectable stage III non–small cell lung cancer (NSCLC), suggests a long-term update of the RTOG 0617 trial.

Initial results of the phase 3 randomized controlled trial, at a median follow-up of 1.9 years, showed that median overall survival was about 8 months longer with the 60-Gy standard dose of radiation compared with a 74-Gy high dose, each given along with paclitaxel and carboplatin (Lancet Oncol. 2015;16:187-99).

The update, now at a median follow-up of 5.1 years and reported in the Journal of Clinical Oncology, recapitulates that finding, again showing a roughly 8-month longer overall survival with the standard dose of radiation. Results continue to show no benefit of adding the anti-EGFR antibody cetuximab (Erbitux) to treatment.

“The 5-year overall survival estimate for the standard-dose radiation arm of RTOG 0617, regardless of cetuximab delivery, was 32.1%. This is among the highest overall survival results of any phase III trial for patients with stage III NSCLC,” noted the investigators, led by Jeffrey D. Bradley, MD, department of radiation oncology, Emory University, Atlanta.

“These results argue strongly that the current standard-of-care radiation dose should be 60 Gy given in 2-Gy daily fractions to a target volume directed at tumor plus margin on the basis of CT and PET/CT, excluding elective nodal irradiation.”

The RTOG 0617 trial was conducted among 496 patients with unresectable stage III NSCLC in the United States and Canada. They were randomized to receive standard-dose or high-dose radiation in addition to concurrent chemotherapy, and randomized again to receive cetuximab or not.

SOURCE: Bradley JD et al. J Clin Oncol. 2019 Dec 16. doi: 10.1200/JCO.19.01162.

More is not better when it comes to radiation therapy administered with concurrent chemotherapy for unresectable stage III non–small cell lung cancer (NSCLC), suggests a long-term update of the RTOG 0617 trial.

Initial results of the phase 3 randomized controlled trial, at a median follow-up of 1.9 years, showed that median overall survival was about 8 months longer with the 60-Gy standard dose of radiation compared with a 74-Gy high dose, each given along with paclitaxel and carboplatin (Lancet Oncol. 2015;16:187-99).

The update, now at a median follow-up of 5.1 years and reported in the Journal of Clinical Oncology, recapitulates that finding, again showing a roughly 8-month longer overall survival with the standard dose of radiation. Results continue to show no benefit of adding the anti-EGFR antibody cetuximab (Erbitux) to treatment.

“The 5-year overall survival estimate for the standard-dose radiation arm of RTOG 0617, regardless of cetuximab delivery, was 32.1%. This is among the highest overall survival results of any phase III trial for patients with stage III NSCLC,” noted the investigators, led by Jeffrey D. Bradley, MD, department of radiation oncology, Emory University, Atlanta.

“These results argue strongly that the current standard-of-care radiation dose should be 60 Gy given in 2-Gy daily fractions to a target volume directed at tumor plus margin on the basis of CT and PET/CT, excluding elective nodal irradiation.”

The RTOG 0617 trial was conducted among 496 patients with unresectable stage III NSCLC in the United States and Canada. They were randomized to receive standard-dose or high-dose radiation in addition to concurrent chemotherapy, and randomized again to receive cetuximab or not.

SOURCE: Bradley JD et al. J Clin Oncol. 2019 Dec 16. doi: 10.1200/JCO.19.01162.

More is not better when it comes to radiation therapy administered with concurrent chemotherapy for unresectable stage III non–small cell lung cancer (NSCLC), suggests a long-term update of the RTOG 0617 trial.

Initial results of the phase 3 randomized controlled trial, at a median follow-up of 1.9 years, showed that median overall survival was about 8 months longer with the 60-Gy standard dose of radiation compared with a 74-Gy high dose, each given along with paclitaxel and carboplatin (Lancet Oncol. 2015;16:187-99).

The update, now at a median follow-up of 5.1 years and reported in the Journal of Clinical Oncology, recapitulates that finding, again showing a roughly 8-month longer overall survival with the standard dose of radiation. Results continue to show no benefit of adding the anti-EGFR antibody cetuximab (Erbitux) to treatment.

“The 5-year overall survival estimate for the standard-dose radiation arm of RTOG 0617, regardless of cetuximab delivery, was 32.1%. This is among the highest overall survival results of any phase III trial for patients with stage III NSCLC,” noted the investigators, led by Jeffrey D. Bradley, MD, department of radiation oncology, Emory University, Atlanta.

“These results argue strongly that the current standard-of-care radiation dose should be 60 Gy given in 2-Gy daily fractions to a target volume directed at tumor plus margin on the basis of CT and PET/CT, excluding elective nodal irradiation.”

The RTOG 0617 trial was conducted among 496 patients with unresectable stage III NSCLC in the United States and Canada. They were randomized to receive standard-dose or high-dose radiation in addition to concurrent chemotherapy, and randomized again to receive cetuximab or not.

SOURCE: Bradley JD et al. J Clin Oncol. 2019 Dec 16. doi: 10.1200/JCO.19.01162.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Most young women with epithelial ovarian cancer can undergo surgery preserving the unaffected ovary and uterus – and thus their fertility – without compromising their survival, a cohort study of more than 9,000 women in Cancer suggests.

“Loss of reproductive capability and surgical menopause can negatively affect survivorship and quality of life among young women with ovarian cancer,” noted the investigators, who were led by Sarah M. Crafton, MD, division of gynecologic oncology, Allegheny Health Network in Pittsburgh. “ASCO has published guidelines to address the importance of implementing fertility preservation counseling as standard of care for all patients of reproductive age with cancer. However, the safety of such procedures should be thoroughly assessed in ongoing analyses.”

Dr. Crafton and colleagues used the Surveillance, Epidemiology, and End Results (SEER) program database and the National Cancer Database (NCDB) to retrospectively identify women 44 years old or younger with a primary epithelial ovarian cancer. The women were classified as having undergone surgery that spared fertility (unilateral salpingo-oophorectomy with uterine preservation) or surgery that did not (bilateral salpingo-oophorectomy with hysterectomy).

Study results, reported in Cancer, were based on 9,017 women – 3,932 from the SEER database and 5,085 from the NCDB – with epithelial ovarian cancer diagnosed between the ages of 15 and 44 years. Median follow-up was 6.5 years in SEER and 4.6 years in NCDB.

Overall, 26.1% of the SEER cohort and 24.8% of the NCDB cohort had undergone fertility-sparing surgery. In both cohorts, odds of this surgery were higher among younger women, those with a more recent ovarian cancer diagnosis, and those who did not receive adjuvant chemotherapy.

Among women with stage II-IV serous epithelial ovarian cancer in the SEER cohort, those who underwent fertility-sparing surgery had poorer overall survival (hazard ratio for death, 1.61; P = .0008). However, fertility-sparing surgery was not significantly associated with survival in other SEER subgroups defined by stage and grade or by stage and histology or in any NCDB subgroup defined by these parameters.

“In general, our findings regarding survival support the current National Comprehensive Cancer Network recommendation that fertility-sparing surgery can be considered as an alternative for traditional, comprehensive staging for those patients who desire fertility, for whom ovarian retention is technically feasible, and who have early-stage disease,” Dr. Crafton and coinvestigators wrote.

“Our observation of an increased risk of death associated with fertility-sparing surgery among women with advanced-stage, serous epithelial ovarian cancer in the SEER population supports the clinical recommendation that the decision to pursue fertility-sparing surgery should be individualized on the basis of patient/provider counseling and disease characteristics,” they concluded.

Dr. Crafton did not report any disclosures. The study was supported by the National Cancer Institute.

SOURCE: Crafton SM et al. Cancer. 2019 Nov 27. doi: 10.1002/cncr.32620.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.

Sequential chemoradiotherapy (CRT) and immunotherapy is safe, well tolerated, and efficacious among patients with locally advanced cervical cancer being treated with curative intent, a multicenter phase 1 trial suggests.

Less than 10% of patients treated with this sequence experienced a grade 3 toxicity. Meanwhile, more than 80% were alive and free of disease progression at 1 year.

“Despite standard CRT, most women with lymph node–positive cervical cancer experience disease recurrence,” note the investigators, led by Jyoti S. Mayadev, MD, associate professor in the department of radiation medicine and applied sciences, University of California, San Diego, in La Jolla. “Our study is potentially transformative in the standard treatment schema of locally advanced cervical cancer, with the prospect for immuno-oncology to add durable survival in patients with node-positive disease, a current unmet oncologic need.”

The investigators enrolled in the trial 32 women from Gynecology Oncology Cooperative Group member institutions who had stage IB2 to IVA cervical cancer with positive pelvic and/or para-aortic lymph nodes. Treatment consisted of six weekly doses of cisplatin, 40 mg/m², concurrent with extended-field, 3-dimensional conformal radiotherapy, followed by the immune checkpoint inhibitor ipilimumab (Yervoy) every 21 days for four cycles.

Results reported in JAMA Oncology showed that all 32 patients completed CRT and 21 patients went on to receive ipilimumab. Among the latter, 86% completed all four planned cycles and the rest completed two cycles.

In the group receiving sequential CRT and ipilimumab, 9.5% experienced grade 3 toxicity (lipase increase in one case and dermatitis in another case). Both toxicities were self-limited.

With a 14.8-month median follow-up, the patients treated with CRT-ipilimumab had a 12-month overall survival rate of 90%, and a 12-month progression-free survival rate of 81% (median durations were not reached). Neither human papillomavirus genotype nor HLA subtype was associated with these outcomes.

Translational analyses showed that patients experienced an increase in peripheral blood T cells expressing programmed cell death 1 (PD-1) after CRT that was then sustained with ipilimumab therapy. “[T]he use of an immune checkpoint inhibitor could stimulate the antitumor activity of tumor-specific cytotoxic T cells and augment radiation-induced neoantigen load,” the investigators proposed.

“To our knowledge, this phase 1 study is the first to show tolerability with a signal of efficacy of an immune check-point inhibitor ... as a part of the definitive treatment of locally advanced cervical cancer,” they concluded. “Our findings show promise for the use of immunotherapy in the definitive setting of locally advanced, node-positive cervical cancer; patients with this cancer historically have a poor prognosis with standard therapy alone.”

Dr. Mayadev disclosed receiving a grant from the National Cancer Institute during the conduct of the study, personal fees from AstraZeneca, grants from NRG Oncology, and personal fees and nonfinancial support from the Gynecology Oncology Group Foundation outside the submitted work; receiving compensation for serving on the advisory board of Varian Medical Systems in 2018; and being a speaker for Samsung Medical Systems in 2017. The study was supported by the National Cancer Institute and by institutional funds.

SOURCE: Mayadev JS et al. JAMA Oncol. 2019 Nov 27. doi: 10.1001/jamaoncol.2019.3857.

The benefit of rituximab maintenance therapy in follicular lymphoma is long lasting and evident out to at least 9 years, according to the final efficacy analysis of the PRIMA phase 3, randomized, controlled trial.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Previously reported results of this pivotal trial showed prolongation of progression-free survival and time to next treatment with rituximab maintenance at a follow-up of 3 years and 6 years.

“Rituximab maintenance is now widely recommended for patients with follicular lymphoma responding to first-line rituximab-based immunochemotherapy,” Emmanuel Bachy, MD, PhD, of Institut National de la Santé et de la Recherche Médicale in Pierre-Bénite, France, and colleagues reported in the Journal of Clinical Oncology.

In PRIMA, patients with previously untreated high–tumor burden follicular lymphoma received any of three immunochemotherapy induction regimens. The 1,018 patients having a response were then randomly assigned to receive 2 years of rituximab (Rituxan) maintenance or observation only.

Dr. Bachy and colleagues performed the trial’s final efficacy analyses, now at a median follow-up of 9 years.

Among the 607 patients consenting to the extended follow-up, median progression-free survival was 10.5 years in the rituximab-maintenance group, compared with 4.1 years in the observation group (hazard ratio, 0.61; P less than .001).

“Subgroup analyses showed the substantial progression-free survival improvement associated with rituximab maintenance was independent of age, sex, induction immunochemotherapy regimen, response to induction, or [Follicular Lymphoma International Prognostic Index] risk score,” the investigators wrote.

Rituximab maintenance also prolonged the median time to next antilymphoma treatment (not reached vs. 6.1 years; hazard ratio, 0.66; P less than .001) and time to next chemotherapy treatment (not reached vs. 9.3 years; hazard ratio, 0.71; P less than .001).

But there was no significant difference in overall survival. Median overall survival was not reached in either group (hazard ratio, 1.04; P = .7948). The estimated 10-year overall survival rate was about 80% in both groups.

“This 9-year follow-up of the PRIMA study demonstrates that rituximab maintenance after induction immunochemotherapy provides a significant long-term [progression-free survival] benefit over observation,” the investigators wrote. “Despite the lack of [overall survival] advantage, it is noteworthy that more than half of the patients in the rituximab maintenance arm remain free of disease progression and have not required new antilymphoma treatment beyond 10 years.”

The trial was sponsored by the Lymphoma Study Association and supported by F. Hoffmann–La Roche and Biogen. Dr. Bachy reported financial disclosures related to Roche and other companies.

SOURCE: Bachy E et al. J Clin Oncol. 2019 Nov 1;37(31):2815-24.

The benefit of rituximab maintenance therapy in follicular lymphoma is long lasting and evident out to at least 9 years, according to the final efficacy analysis of the PRIMA phase 3, randomized, controlled trial.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Previously reported results of this pivotal trial showed prolongation of progression-free survival and time to next treatment with rituximab maintenance at a follow-up of 3 years and 6 years.

“Rituximab maintenance is now widely recommended for patients with follicular lymphoma responding to first-line rituximab-based immunochemotherapy,” Emmanuel Bachy, MD, PhD, of Institut National de la Santé et de la Recherche Médicale in Pierre-Bénite, France, and colleagues reported in the Journal of Clinical Oncology.

In PRIMA, patients with previously untreated high–tumor burden follicular lymphoma received any of three immunochemotherapy induction regimens. The 1,018 patients having a response were then randomly assigned to receive 2 years of rituximab (Rituxan) maintenance or observation only.

Dr. Bachy and colleagues performed the trial’s final efficacy analyses, now at a median follow-up of 9 years.

Among the 607 patients consenting to the extended follow-up, median progression-free survival was 10.5 years in the rituximab-maintenance group, compared with 4.1 years in the observation group (hazard ratio, 0.61; P less than .001).

“Subgroup analyses showed the substantial progression-free survival improvement associated with rituximab maintenance was independent of age, sex, induction immunochemotherapy regimen, response to induction, or [Follicular Lymphoma International Prognostic Index] risk score,” the investigators wrote.

Rituximab maintenance also prolonged the median time to next antilymphoma treatment (not reached vs. 6.1 years; hazard ratio, 0.66; P less than .001) and time to next chemotherapy treatment (not reached vs. 9.3 years; hazard ratio, 0.71; P less than .001).

But there was no significant difference in overall survival. Median overall survival was not reached in either group (hazard ratio, 1.04; P = .7948). The estimated 10-year overall survival rate was about 80% in both groups.

“This 9-year follow-up of the PRIMA study demonstrates that rituximab maintenance after induction immunochemotherapy provides a significant long-term [progression-free survival] benefit over observation,” the investigators wrote. “Despite the lack of [overall survival] advantage, it is noteworthy that more than half of the patients in the rituximab maintenance arm remain free of disease progression and have not required new antilymphoma treatment beyond 10 years.”

The trial was sponsored by the Lymphoma Study Association and supported by F. Hoffmann–La Roche and Biogen. Dr. Bachy reported financial disclosures related to Roche and other companies.

SOURCE: Bachy E et al. J Clin Oncol. 2019 Nov 1;37(31):2815-24.

The benefit of rituximab maintenance therapy in follicular lymphoma is long lasting and evident out to at least 9 years, according to the final efficacy analysis of the PRIMA phase 3, randomized, controlled trial.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Previously reported results of this pivotal trial showed prolongation of progression-free survival and time to next treatment with rituximab maintenance at a follow-up of 3 years and 6 years.

“Rituximab maintenance is now widely recommended for patients with follicular lymphoma responding to first-line rituximab-based immunochemotherapy,” Emmanuel Bachy, MD, PhD, of Institut National de la Santé et de la Recherche Médicale in Pierre-Bénite, France, and colleagues reported in the Journal of Clinical Oncology.

In PRIMA, patients with previously untreated high–tumor burden follicular lymphoma received any of three immunochemotherapy induction regimens. The 1,018 patients having a response were then randomly assigned to receive 2 years of rituximab (Rituxan) maintenance or observation only.

Dr. Bachy and colleagues performed the trial’s final efficacy analyses, now at a median follow-up of 9 years.

Among the 607 patients consenting to the extended follow-up, median progression-free survival was 10.5 years in the rituximab-maintenance group, compared with 4.1 years in the observation group (hazard ratio, 0.61; P less than .001).

“Subgroup analyses showed the substantial progression-free survival improvement associated with rituximab maintenance was independent of age, sex, induction immunochemotherapy regimen, response to induction, or [Follicular Lymphoma International Prognostic Index] risk score,” the investigators wrote.

Rituximab maintenance also prolonged the median time to next antilymphoma treatment (not reached vs. 6.1 years; hazard ratio, 0.66; P less than .001) and time to next chemotherapy treatment (not reached vs. 9.3 years; hazard ratio, 0.71; P less than .001).

But there was no significant difference in overall survival. Median overall survival was not reached in either group (hazard ratio, 1.04; P = .7948). The estimated 10-year overall survival rate was about 80% in both groups.

“This 9-year follow-up of the PRIMA study demonstrates that rituximab maintenance after induction immunochemotherapy provides a significant long-term [progression-free survival] benefit over observation,” the investigators wrote. “Despite the lack of [overall survival] advantage, it is noteworthy that more than half of the patients in the rituximab maintenance arm remain free of disease progression and have not required new antilymphoma treatment beyond 10 years.”

The trial was sponsored by the Lymphoma Study Association and supported by F. Hoffmann–La Roche and Biogen. Dr. Bachy reported financial disclosures related to Roche and other companies.

SOURCE: Bachy E et al. J Clin Oncol. 2019 Nov 1;37(31):2815-24.

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.

A novel 17-gene expression signature may help guide the choice of initial treatment in patients with IGHV-unmutated chronic lymphocytic leukemia (CLL), according to findings of a retrospective dual cohort study.

copyright Kativ/iStockphoto

“[Fludarabine, cyclophosphamide, and rituximab] was the first regimen to improve progression-free survival and overall survival in patients with chronic lymphocytic leukaemia, and has become a gold-standard chemoimmunotherapy regimen in physically fit patients,” wrote the investigators, who were led by Carmen D. Herling, MD, of the Center for Integrated Oncology, Cologne, Germany; and Kevin R. Coombes, PhD, of Ohio State University, Columbus.

While several studies demonstrate that young, fit patients with mutated IGHV gene and no high-risk cytogenetic abnormalities achieve durable remission with the FCR (fludarabine, cyclophosphamide, and rituximab) regimen, there have been no studies to identify if this is true for patients with unmutated IGHV gene, they reported in the Lancet Oncology.

The investigators performed transcriptional profiling using peripheral blood samples collected from two cohorts of patients with CLL who were treated with frontline FCR.

The discovery and training cohort consisted of 101 patients (65% with IGHV-unmutated disease) treated at the MD Anderson Cancer Center who had a median follow-up of about 12 years. The validation cohort consisted of 109 patients with IGHV-unmutated disease treated on the German CLL8 single-arm trial who had a median follow-up of about 6 years.

A total of 1,136 genes showed a significant univariate association with time to progression. Ultimately, 17 of these genes – most of them involved in purine metabolism and oxidative phosphorylation – were included in the expression signature.

Among patients with IGHV-unmutated CLL, the 17-gene signature discriminated between two groups having differing time to progression after their frontline FCR chemoimmunotherapy: an unfavorable prognosis group and an intermediate prognosis group.

The unfavorable prognosis group had a significantly higher relative risk of progression in both the discovery/training cohort (hazard ratio, 3.83; P less than .0001) and the validation cohort (HR, 1.90; P = .008). In the validation cohort, the median time to progression was 39 months among patients with a signature-defined unfavorable prognosis, compared with 59 months among patients with a signature-defined intermediate prognosis.

“We would recommend testing the value of the 17-gene signature in a prospective study that compares FCR treatment with alternative therapies, such as ibrutinib, as part of a randomised clinical trial,” the investigators wrote.

Dr. Herling reported financial disclosures related to Hoffmann-La Roche, and Dr. Coombes reported grants from the National Institutes of Health. The study was funded by the Chronic Lymphocytic Leukaemia Global Research Foundation and the National Institutes of Health/National Cancer Institute.

SOURCE: Herling CD et al. Lancet Oncol. 2019;20(11):1576-86.