Pembrolizumab plus chemotherapy versus placebo plus chemotherapy in patients with advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma enrolled in the Republic of Korea: KEYNOTE-859.
Authors: Sun Young Rha, Jeeyun Lee, Min-Hee Ryu, Lina Yin, Pierre Leconte, Pooja Bhagia, Do-Youn Oh
Journal: Journal of Clinical Oncology (2025)

428 Background: After a median follow-up of 41.6 mo, data from the global phase 3 KEYNOTE-859 study (NCT03675737; N = 1579) continued to show that use of pembrolizumab (pembro) plus chemotherapy (chemo) provided a significant and clinically meaningful improvement in overall survival (OS), with manageable safety, versus placebo (pbo) plus chemo for patients (pts) with locally advanced or metastatic HER2-negative G/GEJ adenocarcinoma. This post hoc analysis evaluated the safety and efficacy of pembro plus chemo in pts enrolled in KEYNOTE-859 in the Republic of Korea. Methods: Eligible pts aged ≥18 years with locally advanced unresectable or metastatic HER2-negative G/GEJ adenocarcinoma, measurable disease per RECIST v1.1, and an ECOG performance status (PS) of 0 or 1 were randomly assigned 1:1 to receive pembro 200 mg or pbo IV Q3W for ≤35 cycles. All pts received investigator’s choice of chemo (FP or CAPOX). The primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per RECIST v1.1 by blinded independent central review, and safety. Efficacy end points were evaluated in all randomly assigned pts (intention to treat). Results: A total of 150 pts (66, pembro plus chemo; 84, pbo plus chemo) from the Republic of Korea were enrolled. The median time from randomization to database cutoff (August 22, 2023) was 48.1 mo (range, 32.7-56.8). Baseline characteristics were generally well balanced between treatment groups. Most pts were male (71.3%) with an ECOG PS of 1 (66.7%); 43.3% of pts had ≥3 metastases. The median OS was 19.5 mo (95% CI, 14.2-26.2) for pembro plus chemo versus 15.2 mo (95% CI, 11.7-19.8) for pbo plus chemo (HR, 0.80; 95% CI, 0.55-1.15). Additional efficacy data are reported in the Table. Treatment-related adverse events occurred in 63 pts (95.5%) in the pembro plus chemo group and 78 pts (92.9%) in the pbo plus chemo group; 39 (59.1%) and 31 (36.9%) pts, respectively, were grade 3 or 4. No treatment-related deaths occurred. Conclusions: Consistent with the global results, clinical outcomes favored pembro plus chemo versus pbo plus chemo with manageable safety in pts from the Republic of Korea with HER2-negative G/GEJ adenocarcinoma enrolled in KEYNOTE-859. Clinical trial information: NCT03675737 . Pembro + chemon = 66 Pbo + chemon = 84 Median PFS (95% CI), mo a 11.0 (6.9-17.6) 7.2 (5.6-8.9) PFS HR (95% CI) b 0.74 (0.48-1.13) ORR, % (95% CI) c 53.0 (40.3-65.4) 46.4 (35.5-57.6) Median DOR (range), mo 15.0 (1.4+ to 50.8+) 6.9 (1.4+ to 44.3+) Responses lasting ≥24 mo, a % 42.6 23.6 a Based on Kaplan-Meier estimates. b Based on the unstratified Cox regression model with the Efron method of tie handling with treatment as a covariate. c Based on the stratified Miettinen and Nurminen method with strata weighting by sample size.