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Clinical Trial
. 2025 Apr;42(4):1892-1906.
doi: 10.1007/s12325-024-03069-4. Epub 2025 Mar 1.

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

Shukui Qin  1   2 , Yuxian Bai  3 , Jin Li  4 , Hongming Pan  5 , Suxia Luo  6 , Yanli Qu  7 , Feng Ye  8 , Lin Yang  9 , Tianshu Liu  10 , Wei Li  11 , Xi Chen  12 , Jianwei Yang  13 , Jieer Ying  14 , Xiaoyan Lin  15 , Lin Zhao  16 , Xinjun Liang  17 , Yixiang Mao  18 , Run Guo  19 , Yi Zuo  19 , Sonal Bordia  20 , Shouguo Li  21
Affiliations
Clinical Trial

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

Shukui Qin et al. Adv Ther. 2025 Apr.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: Clinicaltrials.gov: NCT03675737.

Keywords: China; Gastric adenocarcinoma; Gastroesophageal junction adenocarcinoma; HER2-negative; Pembrolizumab.

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Conflict of interest statement

Declarations. Conflict of Interest: Yixiang Mao is an employee of MSD China, Shanghai, China, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Run Guo and Yi Zuo are employees of MSD China, Beijing, China. Sonal Bordia is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and owns stock in Merck & Co., Inc., Rahway, NJ, USA. Shukui Qin, Yuxian Bai, Jin Li, Hongming Pan, Suxia Luo, Yanli Qu, Feng Ye, Lin Yang, Tianshu Liu, Wei Li, Xi Chen, Jianwei Yang, Jieer Ying, Xiaoyan Lin, Lin Zhao, Xinjun Liang, and Shouguo Li report no conflict of interest. Ethical Approval: The study protocol and amendments, including changes that affected study design, were approved by the appropriate local or national ethics committee at each participating center. All participants provided written informed consent. The study was done in accordance with the Good Clinical Practice requirements outlined by the International Council on Harmonization, the ethical principles of the Declaration of Helsinki, and all local regulations. Institutional review boards or independent ethics committees at each site approved the protocol. The full list of participating sites and ethics committees can be found in the Supplementary Materials Table S5.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates of overall survival in the China subgroup. A ITT population, B PD-L1 CPS ≥ 1 population, and C PD-L1 CPS ≥ 10 population. CPS combined positive score, HR hazard ratio, ITT intention-to-treat, OS overall survival, PD-L1 programmed cell death ligand 1
Fig. 1
Fig. 1
Kaplan–Meier estimates of overall survival in the China subgroup. A ITT population, B PD-L1 CPS ≥ 1 population, and C PD-L1 CPS ≥ 10 population. CPS combined positive score, HR hazard ratio, ITT intention-to-treat, OS overall survival, PD-L1 programmed cell death ligand 1
Fig. 2
Fig. 2
Kaplan–Meier estimates of progression-free survival in the China subgroup. A ITT population, B PD-L1 CPS ≥ 1 population, and C PD-L1 CPS ≥ 10 population. CPS combined positive score, HR hazard ratio, ITT intention-to-treat, PFS progression-free survival, PD-L1 programmed cell death ligand 1
Fig. 2
Fig. 2
Kaplan–Meier estimates of progression-free survival in the China subgroup. A ITT population, B PD-L1 CPS ≥ 1 population, and C PD-L1 CPS ≥ 10 population. CPS combined positive score, HR hazard ratio, ITT intention-to-treat, PFS progression-free survival, PD-L1 programmed cell death ligand 1
See this image and copyright information in PMC

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