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Introduction <p>Tislelizumab + chemotherapy has shown promising results as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). We present long-term safety and efficacy outcomes from the RATIONALE-305 trial after 3 years of follow-up, focusing on the intent-to-treat (ITT) population and subgroups based on programmed death ligand-1 (PD-L1) expression.</p> Methods <p>RATIONALE-305, a randomized, double-blind, placebo-controlled, phase 3 trial conducted across 146 centers in Asia, Europe, and North America (December 2018–February 2024), enrolled 997 adults with human epidermal growth factor receptor 2–negative advanced GC/GEJC, randomized 1:1 to receive tislelizumab + chemotherapy or placebo + chemotherapy. The primary endpoint was overall survival (OS) in patients with PD-L1 Tumor Area Positivity (TAP) score ≥ 5% and the ITT population. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and tolerability. At 3-year follow-up, 959 (96.2%) patients had discontinued or completed treatment. The minimum follow-up duration was 36.6 months.</p> Results <p>In all randomized patients (<i>n</i> = 997), 69.4% male and 30.6% female, tislelizumab + chemotherapy improved OS versus placebo + chemotherapy [15.0 months (95% CI 13.6–16.5) vs. 12.9 months (95% CI 12.1–14.1); stratified hazard ratio (HR) 0.79]. Investigator-assessed PFS was also improved [6.9 months (95% CI 5.7–7.2) vs. 6.2 months (95% CI 5.6–6.9); stratified HR 0.79]. The ORR was higher with tislelizumab + chemotherapy. In patients with a PD-L1 TAP score ≥ 5% [<i>n</i> = 546 (54.8%)], similar OS and PFS benefits were observed compared to the ITT population. OS was 16.4 (95% CI 13.6–19.1) months versus 12.8 (95% CI 12.0–14.5) months, stratified HR 0.71 for tislelizumab + chemotherapy versus placebo + chemotherapy, respectively. PFS was 7.2 (95% CI 5.8–8.4) months versus 5.9 (95% CI, 5.6–7.0) months, stratified HR 0.69. No new safety signals were identified.</p> Conclusion <p>Results from RATIONALE-305 continued to show durable and improved efficacy outcomes with tislelizumab + chemotherapy versus placebo + chemotherapy at 3 years in advanced GC/GEJC, supporting PD-L1 as a potential prognostic biomarker.</p> Trial Registration <p>ClinicalTrials.gov Identifier: NCT03777657.</p>

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Tislelizumab + Chemotherapy in Gastric Cancer: Long-Term RATIONALE-305 Randomized Trial Follow-up

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Marcia Cruz-Correa,
  • Do-Youn Oh,
  • Ken Kato,
  • Josep Tabernero,
  • Yuxian Bai,
  • Jianhua Shi,
  • Keun-Wook Lee,
  • Hidekazu Hirano,
  • David Spigel,
  • Lucjan Wyrwicz,
  • Roberto Pazo Cid,
  • Antonio Cubillo Gracián,
  • Yaling Xu,
  • Tao Sheng,
  • Silu Yang,
  • Rui-Hua Xu,
  • Markus Moehler

摘要

Introduction

Tislelizumab + chemotherapy has shown promising results as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). We present long-term safety and efficacy outcomes from the RATIONALE-305 trial after 3 years of follow-up, focusing on the intent-to-treat (ITT) population and subgroups based on programmed death ligand-1 (PD-L1) expression.

Methods

RATIONALE-305, a randomized, double-blind, placebo-controlled, phase 3 trial conducted across 146 centers in Asia, Europe, and North America (December 2018–February 2024), enrolled 997 adults with human epidermal growth factor receptor 2–negative advanced GC/GEJC, randomized 1:1 to receive tislelizumab + chemotherapy or placebo + chemotherapy. The primary endpoint was overall survival (OS) in patients with PD-L1 Tumor Area Positivity (TAP) score ≥ 5% and the ITT population. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and tolerability. At 3-year follow-up, 959 (96.2%) patients had discontinued or completed treatment. The minimum follow-up duration was 36.6 months.

Results

In all randomized patients (n = 997), 69.4% male and 30.6% female, tislelizumab + chemotherapy improved OS versus placebo + chemotherapy [15.0 months (95% CI 13.6–16.5) vs. 12.9 months (95% CI 12.1–14.1); stratified hazard ratio (HR) 0.79]. Investigator-assessed PFS was also improved [6.9 months (95% CI 5.7–7.2) vs. 6.2 months (95% CI 5.6–6.9); stratified HR 0.79]. The ORR was higher with tislelizumab + chemotherapy. In patients with a PD-L1 TAP score ≥ 5% [n = 546 (54.8%)], similar OS and PFS benefits were observed compared to the ITT population. OS was 16.4 (95% CI 13.6–19.1) months versus 12.8 (95% CI 12.0–14.5) months, stratified HR 0.71 for tislelizumab + chemotherapy versus placebo + chemotherapy, respectively. PFS was 7.2 (95% CI 5.8–8.4) months versus 5.9 (95% CI, 5.6–7.0) months, stratified HR 0.69. No new safety signals were identified.

Conclusion

Results from RATIONALE-305 continued to show durable and improved efficacy outcomes with tislelizumab + chemotherapy versus placebo + chemotherapy at 3 years in advanced GC/GEJC, supporting PD-L1 as a potential prognostic biomarker.

Trial Registration

ClinicalTrials.gov Identifier: NCT03777657.