FDA Amends Pembrolizumab’s Gastric Cancer Indication

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On November 7, the U.S. Food and Drug Administration (FDA) revised the existing indication of pembrolizumab (Keytruda) in combination with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This updated indication—which remains approved under accelerated approval regulations—restricts its use to patients whose tumors express PD-L1 (combined positive score [CPS] of ≥ 1) as determined by an FDA-approved test.

The FDA also approved the Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic device to select patients with gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥ 1).


The efficacy of pembrolizumab in this setting was evaluated in KEYNOTE-811 ( identifier NCT03615326), a multicenter, randomized, double-blind, placebo-controlled trial in patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who have not previously received systemic therapy for metastatic disease. Patients were randomly assigned 1:1 to receive pembrolizumab at 200 mg intravenously or placebo every 2 weeks with trastuzumab, and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The major efficacy outcomes of KEYNOTE-811 are overall survival and progression-free survival. The May 5, 2021, accelerated approval was based on an interim analysis of objective response rate and duration of response. At that time, objective response and duration of response were assessed in the first 264 patients randomly assigned in the trial. Objective response rate was 74% (95% CI = 66%–82%) in the pembrolizumab plus chemotherapy arm and 52% (95% CI = 43%–61%) in the placebo plus chemotherapy arm (P < .0001). The median duration of response was 10.6 months (range = 1.1+ to 16.5+ months) and 9.5 months (range = 1.4+ to 15.4+ months) in the respective arms.

In a recent, prespecified interim analysis of the fully enrolled trial (n = 698), in a subgroup analysis conducted in patients with PD-L1 CPS < 1 (n = 104), the hazard ratios for overall survival and progression-free survival were 1.41 (95% CI = 0.90–2.20) and 1.03 (95% CI = 0.65–1.64), respectively.

The safety profile for participants treated with pembrolizumab and trastuzumab plus chemotherapy in KEYNOTE-811 was generally consistent with the known safety profiles of either trastuzumab plus chemotherapy alone or pembrolizumab monotherapy.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. Pembrolizumab should be administered prior to trastuzumab and chemotherapy when given on the same day.

The FDA approved this application approximately 7 months ahead of the FDA goal date.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.