First-Line Pembrolizumab Plus Chemotherapy for HER2-Negative Advanced Gastric Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-859 Study

Results of the global, randomized, phase 3 KEYNOTE-859 study (N = 1579) showed that first-line pembrolizumab plus chemotherapy produced a statistically significant and clinically meaningful improvement in overall survival (OS) with manageable toxicity versus placebo plus chemotherapy in patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative gastric or gastroesophageal junction cancer. This subgroup analysis was conducted to investigate outcomes in patients enrolled in mainland China. Adults with previously untreated advanced or metastatic HER2-negative gastric cancer or gastroesophageal junction adenocarcinoma were randomly assigned (1:1) to receive pembrolizumab or placebo with fluoropyrimidine- and platinum-containing chemotherapy. The primary outcome was OS. Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR), all assessed per RECIST v1.1 by blinded independent central review, and safety. Overall, 236 patients were enrolled in mainland China (126 pembrolizumab plus chemotherapy; 110 placebo plus chemotherapy). Median time from randomization to database cutoff (October 3, 2022) was 24.7 months (range 15.3–38.9). Median OS was 15.9 months (95% confidence interval [CI] 13.2–19.2) for pembrolizumab plus chemotherapy versus 12.2 months (95% CI 10.6–14.1) for placebo plus chemotherapy (hazard ratio [HR], 0.68; 95% CI 0.50–0.91). Median PFS was 8.1 months (95% CI 6.9–9.6) for pembrolizumab plus chemotherapy versus 5.7 months (95% CI 4.5–6.5) for placebo plus chemotherapy (HR, 0.65; 95% CI 0.48–0.88). ORR was 69.0% for pembrolizumab plus chemotherapy versus 45.5% for placebo plus chemotherapy; median DOR was 8.2 months (range 1.2+ to 34.6+) versus 5.5 months (range 1.3+ to 31.2+), respectively. Grade 3–5 treatment-related adverse events occurred in 82 patients (65.6%) treated with pembrolizumab plus chemotherapy and 54 patients (49.1%) treated with placebo plus chemotherapy. Consistent with efficacy in the overall population from KEYNOTE-859, first-line pembrolizumab plus chemotherapy showed improved efficacy, versus placebo plus chemotherapy, and manageable safety in patients enrolled in mainland China. Clinicaltrials.gov: NCT03675737.