The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor pembrolizumab (Keytruda, Merck) with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of adult patients with locally advanced unresectable or metastatic, human epidermal growth factor receptor (HER2)–negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The approval was based on results from the phase 3 KEYNOTE-859 trial, which showed that adding pembrolizumab to chemotherapy led to a statistically significant improvement in overall survival and progression-free survival (PFS). The results of the trial were published online last month in The Lancet.
This marks the second approval for pembrolizumab to treat gastric cancer. The first approval included patients with HER2-positive gastric or GEJ adenocarcinoma whose tumors express programmed death ligand 1 (PD-L1), as determined by an FDA-approved test.
KEYNOTE-859 enrolled 1579 patients with HER2-negative advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. Patients were randomly allocated to receive pembrolizumab or placebo with combination chemotherapy (cisplatin/5-flurouracil or oxaliplatin/capecitabine).
At a median follow-up of 31 months, patients who received pembrolizumab had significantly improved overall survival vs those who did not receive pembrolizumab (12.9 vs 11.5 months; hazard ratio [HR], 0.78; P < .0001). Median PFS was also significantly longer in the pembrolizumab arm (6.9 vs 5.6 months; HR, 0.76; P < .0001).
The overall response rate was 51% with pembrolizumab and 42% with placebo (P < .0001) and median duration of response was 8 months vs 5.7 months, respectively.
An additional prespecified analysis demonstrated a statistically significant improvement in overall survival, PFS, and overall response rate in patients receiving pembrolizumab who have tumors expressing PD-L1 with a combined positive score ≥ 1 or ≥ 10.
Adverse reactions led to 15% of patients stopping pembrolizumab.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity. Pembrolizumab should be administered before chemotherapy when given on the same day, the FDA said.
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