The FDA has provided traditional approval to pembrolizumab (Keytruda) plus trastuzumab, fluoropyrimidine-, and platinum-based chemotherapy for the initiation of treatment in adult patients with HER2-positive gastric or GEJ adenocarcinoma with PD-L1 expression (CPS ≥ 1). It was previously approved in May 2021, under accelerated approval, on the basis of interim results from the KEYNOTE-811 trial.
The authorization is supported by findings from the KEYNOTE-811 trial, an open-label, double-blind, placebo-controlled randomized trial involving 698 patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma. Out of 698 patients, 594 (85%) patients had PD-L1-positive tumors. Patients were randomized to receive a placebo or pembrolizumab, along with trastuzumab and chemotherapy.
The results showed a statistically significant increase in progression-free survival (10.9 months vs 7.3 months) and overall survival (20.1 months vs 15.7 months) in the pembrolizumab group when compared to the placebo group. In addition, the overall response rate was higher in the pembrolizumab group (73% vs 58%) with a more extended median duration of response (11.3 months vs 9.6 months). The safety profile was in line with previous trials.
The dose of pembrolizumab to be used is 200 mg every 3 weeks or 400 mg every 6 weeks with trastuzumab and chemotherapy. This indication is in line with the FDA’s Project FrontRunner initiative to advance early-line therapies for late-stage cancers. The drug was also granted Orphan Drug designation and utilized the FDA’s Assessment Aid for streamlined evaluation.
