Pembrolizumab with chemo approved for HER2-negative gastric or GEJ adenocarcinoma

On November 16, 2023, the Food and Drug Administration approved Merck’s pembrolizumab — Keytruda — with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction, or GEJ, adenocarcinoma. Efficacy was evaluated in KEYNOTE-859, a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1579 patients with HER2-negative advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. The major efficacy outcome measure was overall survival. Additional secondary efficacy outcome measures included progression free survival, overall response rate, and duration of response as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Treatment with pembrolizumab and chemotherapy resulted in a statistically significant improvement in OS, PFS, and ORR. An additional pre-specified analysis showed a statistically significant improvement in OS, PFS, and ORR in patients receiving pembrolizumab based on tumors expressing PD-L1 CPS greater than or equal to 1 and CPS greater than or equal to 10. Permanent discontinuation of pembrolizumab due to adverse reactions occurred in 15% of patients. Adverse reactions resulting in permanent discontinuation in greater than or equal to 1% were infections and diarrhea.