FDA approves pembrolizumab with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma

Regulatory approval: On Nov 16, 2023, the FDA approved pembrolizumab plus fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Approval was supported by KEYNOTE-859 (n=1579), which showed statistically significant improvements in overall survival, progression-free survival, and overall response rate versus placebo plus chemotherapy. Recommended dosing is 200 mg every 3 weeks or 400 mg every 6 weeks.

Regulatory approval (FDA) — Nov 16, 2023

The FDA approved pembrolizumab (Keytruda) in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Supporting evidence: KEYNOTE-859 (NCT03675737)

KEYNOTE-859 was a multicenter, randomized, double-blind, placebo-controlled trial enrolling 1579 patients with HER2-negative advanced gastric/GEJ adenocarcinoma without prior systemic therapy for metastatic disease. Patients were randomized 1:1 to pembrolizumab 200 mg or placebo with investigator’s choice of FP (cisplatin + 5-FU) or CAPOX (oxaliplatin + capecitabine) every 21 days.

  • Primary endpoint (OS): median OS 12.9 vs 11.5 months (HR 0.78, 95% CI 0.70–0.87; p<0.0001).
  • PFS: 6.9 vs 5.6 months (HR 0.76, 95% CI 0.67–0.85; p<0.0001).
  • ORR: 51% vs 42% (p<0.0001); median DOR 8.0 vs 5.7 months.

A prespecified analysis reported statistically significant improvements in OS/PFS/ORR in tumors with PD-L1 CPS ≥1 and CPS ≥10.

Safety and dosing (from FDA communication)

Permanent discontinuation due to adverse reactions occurred in 15%; ≥1% causes included infections and diarrhea. Recommended pembrolizumab dosing: 200 mg Q3W or 400 mg Q6W until progression or unacceptable toxicity; administer pembrolizumab before chemotherapy when given on the same day.

The review was conducted under Project Orbis; reviews at partner agencies were ongoing at the time of the FDA communication.

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