ESMO 2023: Pembrolizumab Improves PFS With Standard Treatment in HER2-Positive Gastroesophageal Cancer
Treatment can be considered for first-line therapy in patients with PD-L1 overexpression
FRIDAY, Oct. 27, 2023 (HealthDay News) -- Pembrolizumab improved progression-free survival (PFS) when combined with trastuzumab and chemotherapy for firstline treatment of metastatic HER2-positive gastroesophageal cancer, according to study findings published online Oct. 20 in The Lancet to coincide with the annual meeting of the European Society for Medical Oncology, held from Oct. 20 to 24 in Madrid, Spain.
“For more than a decade, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy has been the first-line therapy for patients with HER2-positive gastric or gastro-esophageal junction adenocarcinomas,” write Yelena Y. Janjigian, M.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues. “Although checkpoint inhibitors in combination with chemotherapy are an effective treatment option for patients with HER2-negative gastric or gastro-esophageal junction cancer, data on their effect in combination with standard therapy for treatment of HER2-positive gastric or gastro-esophageal junction cancer are scarce.”
The researchers evaluated data from the randomized, phase 3 KEYNOTE-311 trial, which included patients from 168 medical centers across 20 countries. Patients aged 18 years and older with locally advanced or metastatic HER2-positive gastroesophageal junction adenocarcinoma, without previous treatment, were randomly assigned 1:1 to pembrolizumab 200 mg or placebo, in combination with standard chemotherapy plus trastuzumab every three weeks for up to 35 cycles.
The study included 698 patients. At the second interim analysis, the researchers found the median PFS was 10 months in the pembrolizumab group compared with 8.1 months in the placebo group (hazard ratio [HR], 0.72; 95 percent confidence interval [CI], 0.60 to 0.87). Median overall survival (OS) was 20 months in the pembrolizumab group versus 16.9 months in the placebo group (P = 0.084).
At the third interim analysis, 82 percent of patients in the pembrolizumab group and 88 percent of patients in the placebo group discontinued treatment, primarily because of disease progression. The median PFS was 10 months in the pembrolizumab group compared with 8.1 months in the placebo group (HR, 0.73; 95 percent CI, 0.61 to 0.87). Median OS was 20 months in the pembrolizumab group versus 16.8 months in the placebo group (HR, 0.84; 95 percent CI, 0.70 to 1.01).
Grade 3 or worse treatment-related adverse events occurred in 58 percent of patients in the pembrolizumab group versus 51 percent of the placebo group. The most common adverse events were diarrhea, nausea, and anemia.
“These data support the use of first-line anti-PD-1 therapy in combination with trastuzumab in first-line HER2-positive gastric or gastro-esophageal junction cancer and are the first to show a progression-free survival improvement over standard of care in this patient population,” the authors write. “The effect of this regimen on progression-free survival suggests that it could be considered as a first-line therapy option for patients with metastatic gastro-esophageal cancer with co-occurring HER2 and PD-L1 overexpression; however, the overall survival benefit of this regimen is yet to be determined.”
Several authors disclosed financial ties to the pharmaceutical industry, including Merck, which funded the study.
Abstract/Full Text (subscription or payment may be required)
Click on any of these tags to subscribe to Topic Alerts. Once subscribed, you can get a single, daily email any time PracticeUpdate publishes content on the topics that interest you.
Visit your Preferences and Settings section to Manage All Topic Alerts