by Elana Gotkine

For patients with HER2-positive gastroesophageal junction (GEJ) adenocarcinoma, pembrolizumab improves progression-free survival when combined with chemotherapy and trastuzumab, according to a study published online Oct. 20 in The Lancet. The research was published to coincide with the annual meeting of the European Society for Medical Oncology, held from Oct. 20 to 24 in Madrid.

Yelena Y. Janjigian, M.D., from Memorial Sloan Kettering Cancer Center in New York City, and colleagues conducted a randomized trial involving adult patients with locally advanced or metastatic HER2-positive gastroesophageal junction adenocarcinoma without previous first-line treatment from 168 medical centers in 20 countries. Participants were randomly assigned to intravenous pembrolizumab 200 mg or placebo (350 and 348, respectively), both combined with standard chemotherapy plus trastuzumab.

The researchers found that at the third interim analysis, 82 and 88 percent of patients in the pembrolizumab and placebo groups, respectively, had discontinued treatment, mainly due to disease progression.

Median progression-free survival was 10.0 and 8.1 months in the pembrolizumab and placebo groups, respectively, at the second interim analysis (median follow-up, 28.3 and 28.5 months; hazard ratio, 0.72; 95 percent confidence interval, 0.60 to 0.87). Median overall survival was not significantly different between the groups (20.0 and 16.9 months, respectively; hazard ratio, 0.87; 95 percent confidence interval, 0.72 to 1.06).

Median progression-free survival was 10.0 and 8.1 months, respectively, at the third interim analysis (median follow-up, 38.4 and 38.6 months; hazard ratio, 0.73; 95 percent confidence interval, 0.61 to 0.87), and median overall survival was 20.0 and 16.8 months, respectively (hazard ratio, 0.84; 95 percent confidence interval, 0.70 to 1.01), which did not meet the prespecified criteria for significance.

"The final overall survival analysis is needed to establish the long-term therapeutic effect of this regimen," the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Merck, which manufactures pembrolizumab and funded the study.

More information: Yelena Y Janjigian et al, Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial, The Lancet (2023). DOI: 10.1016/S0140-6736(23)02033-0

Elizabeth C Smyth et al, Combining chemotherapy, trastuzumab, and immune-checkpoint inhibitors in HER2-positive gastro-oesophageal cancer, The Lancet (2023). DOI: 10.1016/S0140-6736(23)02296-1

Journal information: The Lancet 

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