Pembrolizumab Gets Nod for HER2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1 (CPS ≥1)

Officials with the FDA have granted traditional approval to pembrolizumab (Keytruda; Merck) with trastuzumab- (Herceptin; Genentech), fluoropyrimidine-, and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express programmed death-ligand 1 (PD-L1) with a combined positive score (CPS) ≥1.¹

The latest approval was granted on March 19, 2025, but pembrolizumab was previously granted accelerated approval for this indication on May 5, 2021, based on interim analysis data from KEYNOTE-811 (NCT03615326), a multicenter, double-blind, placebo-controlled trial that enrolled 698 patients with HER2-positive advanced gastric or GEJ adenocarcinoma not previously treated with systemic therapy for metastatic disease. Patients were randomly assigned to pembrolizumab 200 mg or placebo, in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

Researchers noted a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) demonstrated in patients who were randomly assigned to pembrolizumab in combination with trastuzumab and chemotherapy compared with placebo in combination with trastuzumab and chemotherapy. In patients with tumors that were PD-L1 with CPS ≥1, the median PFS was 10.9 months (95% confidence interval [CI], 8.5-12.5) in the pembrolizumab arm compared with 7.3 months (95% CI, 6.8-8.4) in the placebo arm (hazard ratio [HR] 0.72 [95% CI, 0.60-0.87]). Median OS was 20.1 months (95% CI, 17.9-22.9) and 15.7 months (95% CI, 13.5-18.5) in the respective arms (HR 0.79 [95% CI, 0.66-0.95]. ORR was 73% (95% CI, 68-78) and 58% (95% CI, 53-64), and median duration of response was 11.3 months (95% CI, 9.9-13.7) and 9.6 months (95% CI, 7.1-11.2).

The adverse-reaction profile observed in patients receiving pembrolizumab was consistent with the known pembrolizumab safety profile.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks in combination with trastuzumab and chemotherapy.

Reference

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