Pembrolizumab Plus Chemotherapy Approved for Patients With HER2-Negative Gastric or Gastroesophageal Junction Cancer

The US Food and Drug Administration (FDA) has approved pembrolizumab plus fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This regulatory decision was based on the results of the multicenter, randomized, double-blind, placebo-controlled KEYNOTE-859 trial. This trial enrolled 1579 patients with HER2-negative advanced gastric or GEJ adenocarcinoma who had not previously received any systemic treatment for metastatic disease. Patients were randomized on a 1-to-1 basis to receive either 200mg pembrolizumab or placebo, plus investigator’s choice of chemotherapy (cisplatin plus 5-FU or oxaliplatin plus capecitabine). The main end point was overall survival (OS), with additional outcomes including progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR).

Pembrolizumab plus chemotherapy demonstrated a statistically significant improvement of OS, PFS, and ORR, vs placebo plus chemotherapy. The median OS in the pembrolizumab arm was 12.9 months, compared with 11.5 months in the placebo arm (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70 to 0.87); P < .0001). The median PFS was 6.9 months and 5.6 months, respectively (HR, 0.76; 95% CI, 0.67 to 0.85; P < .0001). The median ORR was 51% and 42%; the median DOR was 8 months and 5.7 months, in the respective arms. An additional analysis showed a statistically significant improvement of OS, PFS, and ORR among patients in the pembrolizumab arm with tumors expression PD-L1 CPS ≥1 and CPS ≥10.

Discontinuation of pembrolizumab from adverse reactions occurred in 15% of patients, with those adverse events most commonly (≥1%) being infections and diarrhea.

The FDA recommends 200 mg of pembrolizumab every 3 weeks, or 400 mg every 6 weeks until disease progression or unacceptable tolerability. When administered on the same day as chemotherapy, pembrolizumab should be given first.

Source:

FDA approves pembrolizumab with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma. US Food and Drug Administration. Published November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-her2-negative-gastric-or-gastroesophageal-junction