On November 16, 2023, pembrolizumab (Keytruda) was approved with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.1
Supporting Efficacy Data
Approval was based on the multicenter double-blind KEYNOTE-859 trial (ClinicalTrials.gov identifier NCT03675737), in which 1,579 patients were randomly assigned to pembrolizumab at 200 mg every 3 weeks (n = 790) or placebo (n = 789) plus investigator’s choice of cisplatin at 80 mg/m2 plus fluorouracil at 800 mg/m2/d for 5 days or oxaliplatin at 130 mg/m2 on day 1 plus capecitabine at 1,000 mg/m2 twice daily for 14 days of each 21-day cycle.
OF NOTE
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity
The median overall survival was 12.9 months (95% confidence interval [CI] = 11.9–14.0 months) in the pembrolizumab group vs 11.5 months (95% CI = 10.6–12.1 months) in the control group (hazard ratio [HR] = 0.78, 95% CI = 0.70–0.87, P < .0001). Median progression-free survival was 6.9 months (95% CI = 6.3–7.2 months) vs 5.6 months (95% CI = 5.5–5.7 months; HR = 0.76, 95% CI = 0.67–0.85, P < .0001). Objective response rates were 51% vs 42% (P < .001), and median durations of response were 8 months vs 5.7 months. Prespecified analysis showed significant improvements in overall survival, progression-free survival, and objective response in the pembrolizumab group among patients with a PD-L1 combined positive score ≥ 1 (78% of patients) and a combined positive score ≥ 10.
How It Is Used
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 prior to chemotherapy when given on the same day.
Safety Profile
In KEYNOTE-859, the most common grade 3 or 4 adverse events in the pembrolizumab group included fatigue (8%), diarrhea (6%), peripheral neuropathy (5%), and vomiting (5%). The most common grade 3 or 4 laboratory abnormalities were neutropenia (25%) and lymphopenia (20%). Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
REFERENCE
1. Keytruda (pembrolizumab) injection, for intravenous use, prescribing information, Merck & Co, November 2023. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s143lbl.pdf. Accessed December 11, 2023.
