First-line tislelizumab plus chemotherapy in gastric/gastroesophageal junction cancer: RATIONALE305 Asian subgroupAuthors: Ken Kato,1* Yuxian Bai,2 Jianhua Shi,3 Keun-wook Lee,4 Jufeng Wang,5 Hongming Pan,6 Sun
Young Rha,7 Ruixing Zhang,8 Hidekazu Hirano,1 Kensei Yamaguchi,9 Zengqing Guo,10 Yi Ba,11 LeiYang,12 Hiroshi Tsukuda,13 Yaling Xu,14 Tao Sheng,15 Silu Yang,14 Liyun Li,14 Do-Youn Oh,16 Rui-hua Xu,17Affiliations: 1National Cancer Center Hospital, Tokyo, Japan; 2Harbin Medical University Cancer
Hospital, Harbin, China; 3Linyi Cancer Hospital, Linyi, China; 4Seoul National University College ofMedicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 5Henan CancerHospital, Zhengzhou, China; 6Sir Run Run Shaw Hospital, Zhejiang University School of Medicine,Hangzhou, China; 7Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea;
8Fourth Hospital of Hebei Medical University, Shijiazhuang, China; 9Cancer Institute Hospital of JFCR,Tokyo, Japan; 10Fujian Cancer Hospital, Fuzhou, China; 11 Tianjin Medical University Cancer Institute &Hospital, Tianjin, China; 12Nantong Cancer Hospital, Nantong, China; 13Izumi Municipal Hospital,Izumi, Japan; 14BeiGene (Beijing) Co., Ltd, Beijing, China; 15BeiGene, Ltd, Boston, MA, United States;
16Seoul National University Hospital, Cancer Research Institute, Seoul National University College ofMedicine, Seoul, Republic of Korea; 17Sun Yat-sen University Cancer Center State Key Laboratory ofOncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
ABSTRACT
Background: Survival outcomes with platinum + fluoropyrimidine chemotherapy (chemo) alone as
first-line (1L) therapy for advanced gastric/gastroesophageal junction cancer (GC/GEJC) are poor.
Tislelizumab (TIS), an anti- programmed cell death protein-1 antibody, + chemo, showed significant
overall survival (OS) benefit versus placebo (PBO) + chemo as 1L therapy in patients (pts) withadvanced GC/GEJC in the randomized, double-blind, global phase 3 RATIONALE-305 study(NCT03777657). Here, we present results from the Asian pt subgroup analysis.
Methods: Eligible pts were randomized (1:1) to receive TIS 200 mg intravenously every 3 weeks plus
investigator- chosen chemo (ICC [oxaliplatin + capecitabine or 5-fluorouracil + cisplatin]) or PBO + ICC
until disease progression, or intolerable toxicity. Dual primary endpoints were OS in both theprogrammed death ligand-1 (PD-L1)+ (tumor area positivity ≥5%) and intention-to-treat (ITT) analysis
sets. Secondary endpoints included progression-free survival, objective response rate, duration ofresponse, and safety.
Results: 748 pts (TIS + chemo: n=376, PBO + chemo: n=372, of N=997) enrolled from Asia (China,Korea and Japan) were analyzed, including 403 pts in the PD-L1+ analysis set. At final analysis, TIS +chemo showed improvements versus PBO + chemo in OS both in PD-L1+ (median [m] OS: 18.0 [95%confidence interval (CI): 15.0, 21.6] versus 14.0 mo [95% CI: 12.3, 15.5], hazard ratio [HR]=0.71 [95%CI: 0.56, 0.89]) and ITT analysis set (mOS: 16.4 [95% CI: 14.4, 18.0] versus 14.1 mo [95% CI: 12.8,15.4], HR=0.83 [95% CI: 0.70, 0.97]). Incidences of grade ≥3 treatment-related adverse events(TRAEs) were 55.5% versus 50.0% and TRAEs leading to death were 2.4% versus 0.8% for TIS versus
PBO, respectively. TRAEs leading to discontinuation were reported in 17.1% pts in TIS + chemo arm
versus 8.9% patients in PBO + chemo arm.
Conclusion: TIS + chemo produced a clinically meaningful improvement in OS versus PBO + chemo
and a safety profile in pts with advanced GC/GEJC in the Asian subgroup that was consistent withpublished results in the overall study population.

APGCS 2024