On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval for
pembrolizumab (
Keytruda, Merck & Co., Inc., Whitehouse Station, NJ) for the treatment of patients with recurrent, locally advanced or metastatic, gastric or gastroesophageal junction (GEJ)
adenocarcinoma with
disease progression on or after two or more systemic
therapies, including fluoropyrimidine- and
platinum-containing
chemotherapy and, if appropriate, HER2/neu-targeted
therapy, and whose
tumors express
programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test. Approval was based on demonstration of durable overall response rate (ORR) in a multicenter, open-label, multicohort trial (KEYNOTE-059/Cohort 1) that enrolled 259 patients with locally advanced or metastatic gastric or GEJ
adenocarcinoma. Among the 55% (n = 143) of patients whose
tumors expressed PD-L1 based on a combined positive score ≥1 and either were microsatellite stable or had undetermined
microsatellite instability or mismatch repair status, the confirmed ORR as determined by blinded independent central review was 13.3% (95% CI, 8.2-20.0); 1.4% had complete responses. Response durations ranged from 2.8+ to 19.4+ months; 11 patients (58%) had response durations of 6 months or longer, and 5 patients (26%) had response durations of 12 months or longer. The most common (≥20%) adverse reactions of
pembrolizumab observed in KEYNOTE-059/Cohort 1 were
fatigue, decreased appetite,
nausea, and
constipation. The most frequent (≥2%) serious
adverse drug reactions were
pleural effusion,
pneumonia,
dyspnea,
pulmonary embolism, and
pneumonitis.
Pembrolizumab was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx test (Dako, Agilent, Santa Clara, CA) for selection of patients with
gastric cancer for treatment with
pembrolizumab based on PD-L1
tumor expression. IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for Food and Drug Administration approval of
pembrolizumab for the treatment of patients with locally advanced or metastatic gastric or GEJ
adenocarcinoma whose
tumors express PD-L1. The report discusses the basis for limiting the indication to patients with PD-L1-expressing
tumors and the basis for recommending that PD-L1 status be assessed using a fresh
tumor specimen if PD-L1 expression is not detected in an archival gastric or GEJ
cancer specimen.