User login
SAN FRANCISCO – suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.
“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”
The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)
Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.
“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”
“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
Still fit for treatment
The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.
“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”
At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.
“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
Study details
Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.
In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.
Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.
In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.
Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.
The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.
The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.
Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.
SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.
SAN FRANCISCO – suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.
“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”
The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)
Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.
“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”
“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
Still fit for treatment
The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.
“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”
At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.
“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
Study details
Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.
In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.
Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.
In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.
Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.
The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.
The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.
Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.
SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.
SAN FRANCISCO – suggests a preplanned subgroup analysis of the global phase 3 randomized controlled TAGS trial. Results were reported at the 2019 GI Cancers Symposium.
“The standard of care for early-stage gastric cancer is surgery, which is the only potentially curative treatment,” noted lead investigator David H. Ilson, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York. “Forty percent of patients with metastatic disease have had a history of previous gastrectomy.”
The TAGS trial assessed efficacy of combined trifluridine and tipiracil (Lonsurf) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens. (This combination chemotherapy is currently approved in the United States as later-line therapy for metastatic colorectal cancer.)
Compared with placebo, trifluridine/tipiracil prolonged overall survival by 2.6 months in the subgroup who had previously undergone gastrectomy, a benefit slightly greater than the 2.1 months previously reported for the entire trial population (Lancet Oncol. 2018;19:1437-48). And although the gastrectomy subgroup experienced more grade 3 or 4 adverse events, they were not more likely to stop treatment because of toxicity.
“The data from this analysis reinforce the benefit for trifluridine/tipiracil as prolonging survival versus placebo, and this is regardless of prior gastrectomy,” Dr. Ilson summarized. “Hematologic adverse events, such as neutropenia and leukopenia, may have been somewhat more frequent among the trifluridine/tipiracil–treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations. Exposure to the drug was similar between patients with gastrectomy and those in the overall population.”
“Trifluridine/tipiracil is an effective treatment option with a manageable toxicity profile for patients with metastatic gastric cancer, regardless of prior gastrectomy status,” he concluded.
Still fit for treatment
The disconnect between toxicity and treatment discontinuation seen in the TAGS trial is not new, according to invited discussant Martine Extermann, MD, PhD, leader of the Senior Adult Oncology Program at the Moffitt Cancer Center in Tampa. Previous data among geriatric cancer patients have similarly shown that, despite substantial chemotherapy toxicity, by and large, there are only modest effects on health-related quality of life, performance status, and instrumental activities of daily living, she noted.
“The CTCAE [Common Terminology Criteria for Adverse Events] toxicity differences do not always translate into functional impact and treatment cessation. So this is only part of the picture. It’s a convenient part. It’s easily measurable. It’s well acknowledged as a measurement of side effects. But it does not tell the whole story. Quality of life and functional status add to the picture,” Dr. Extermann elaborated. “What the TAGS study is telling us is, despite a gastrectomy, these patients can be treated as a third-line treatment population for gastric cancer, which is not necessarily obvious to every oncologist.”
At the same time, she added that it would be helpful to have nutritional data on the study patients – and on all patients in similar trials, for that matter – because nutritional status is one of the components of the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score used to predict chemotherapy toxicity in older adults.
“I would support that [trifluridine/tipiracil] is an effective third-line chemotherapy in gastric cancer patients with or without prior gastrectomy, and this can be given safely,” Dr. Extermann concluded.
Study details
Patients in TAGS were randomized 2:1 to trifluridine/tipiracil (formerly TAS-102) or placebo, each added to best supportive care. (Trifluridine is a novel oral thymidine analogue, and tipiracil prevents trifluridine degradation.) Overall, 44% had undergone gastrectomy before entering the trial.
In the entire trial population, overall survival was 5.7 months with trifluridine/tipiracil and 3.6 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.56-0.85; P = .0006), as previously reported.
Among the subgroup who had undergone prior gastrectomy, overall survival was 6.0 months with trifluridine/tipiracil and 3.4 months with placebo (HR, 0.57; 95% CI, 0.41-0.79), Dr. Ilson reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The combination also netted better progression-free survival (2.2 vs. 1.8 months; HR, 0.48; 95% CI, 0.35-0.65). “These data mirror the data seen in the overall treatment population,” he commented.
In a multivariate analysis including all prespecified factors, prior gastrectomy was neither prognostic nor predictive. Moreover, the treatment effect size remained the same after adjustment for potential prognostic factors.
Exposure to trifluridine/tipiracil was similar for the gastrectomy subgroup and the entire trial population in terms of relative dose intensity, median number of cycles, and treatment duration.
The rate of grade 3 or 4 treatment-related adverse events with trifluridine/tipiracil in the gastrectomy subgroup, 64%, was higher than that in the entire trial population, 53%, but the rate of discontinuation because of any-grade adverse events was similar, at 10% and 13%, respectively.
The difference in grade 3 or 4 adverse events between the gastrectomy subgroup and the entire trial population was mainly driven by higher rates of neutropenia (44% vs. 34%) and leukopenia (14% vs. 9%) in the former.
Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.
SOURCE: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.
REPORTING FROM THE 2019 GI CANCERS SYMPOSIUM
Key clinical point: Patients with metastatic gastric cancer experience largely similar efficacy and safety outcomes with oral trifluridine/tipiracil regardless of prior gastrectomy.
Major finding: Compared with placebo, trifluridine/tipiracil improved overall survival in the gastrectomy subgroup (hazard ratio, 0.57) with a higher rate of grade 3/4 adverse events in that subgroup (64% vs. 53%) but similar rate of discontinuation because of adverse events (10% vs. 13%).
Study details: Preplanned subgroup analysis of a phase 3 randomized controlled trial (TAGS trial) among 507 patients with metastatic gastric or gastroesophageal junction cancer who had received at least two prior chemotherapy regimens.
Disclosures: Dr. Ilson disclosed that he has a consulting role with Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, Pieris, Roche/Genentech, and Taiho and that he receives research support from Taiho. The study was funded by Taiho Oncology and Taiho Pharmaceutical.
Source: Ilson DH et al. 2019 GI Cancers Symposium, Abstract 3.