Pembrolizumab Combo Boosts Survival in HER2+ Gastric/GEJ Cancer

Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, discusses the long-term survival data from the KEYNOTE-811 trial (NCT03615326) of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and chemotherapy for the treatment of patients with HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The FDA recently granted standard approval to the combination for the treatment of patients with HER2-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, based on data from the KEYNOTE-811 trial.

“We always want to see long-term follow-up, the 2-year follow-up, and the 3-year follow-up, but most importantly, we were waiting for the final overall survival analysis, because the interim analyses were powered to detect differences, but most of the power was spent on response rate and progression-free survival. Progression-free survival was a key end point,” says Janjigian.

According to findings from the phase 3 KEYNOTE-811 trial, the combination of pembrolizumab, trastuzumab, and chemotherapy led to a clinically meaningful and statistically significant improvement in overall survival (OS) vs placebo in patients with HER2-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, meeting the primary end point of the study.² In the pembrolizumab vs placebo arms, the median OS was 20.1 months (95% CI, 17.9-22.9) vs 15.7 months (95% CI, 13.5-18.5).^2,3

REFERENCES:

1. FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). News release. FDA. March 19, 2025. Accessed March 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma

2. Merck announces phase 3 KEYNOTE-811 trial met dual primary endpoint of overall survival (OS) as first-line treatment in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. May 1, 2024. Accessed April 1, 2025. https://tinyurl.com/bdvc86tw

3. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Survival results from the phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study. Ann Oncol. 2023;34(suppl 2):S851-S852. doi:10.1016/j.annonc.2023.09.1424