FDA
Keytruda gains traditional approval for HER2-positive gastric/GEJ cancer
FDA granted traditional approval to Keytruda (pembrolizumab) with trastuzumab, 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 PD-L1 (CPS ≥1).
Efficacy
Conversion to traditional approval was based on data from KEYNOTE-811 (NCT03615326), a multicenter, randomized, double-blind, placebo-controlled trial enrolling 698 patients with HER2-positive advanced gastric or GEJ adenocarcinoma not previously treated with systemic therapy for metastatic disease. Among the 698 patients, 594 (85%) had tumors expressing PD-L1 with a CPS ≥1. Patients were randomized (1:1) to pembrolizumab 200 mg or placebo, in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The major efficacy outcome measures assessed were progression-free survival (PFS) and overall survival (OS). Additional outcome measures included overall response rate (ORR) and duration of response (DOR). A statistically significant improvement in OS and PFS was demonstrated in patients randomized 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 CPS≥1, median PFS was 10.9 months (95% confidence interval [CI], 8.5- 12.5) in the pembrolizumab arm and 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 DOR was 11.3 months (95% CI, 9.9-13.7) and 9.6 months (95% CI, 7.1-11.2).
Safety
The adverse reaction profile observed in patients receiving pembrolizumab was consistent with the known safety profile of the drug.
Recommended dose
The recommended dosage of pembrolizumab is 200 mg q3wks or 400 mg q6wks in combination with trastuzumab and chemotherapy.
Sources:
FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). [News release]. U.S. Food and Drug Administration. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma