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

Area of Science:

• Oncology
• Immunotherapy
• Gastrointestinal Cancers

Background:

• Advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) remains a significant health challenge.
• Tislelizumab, an immune checkpoint inhibitor, combined with chemotherapy shows promise in early-phase studies for GC/GEJC.
• Long-term safety and efficacy data are crucial for establishing first-line treatment standards.

Purpose of the Study:

• To present 3-year follow-up safety and efficacy outcomes of tislelizumab plus chemotherapy versus placebo plus chemotherapy in the RATIONALE-305 trial.
• To evaluate treatment effects in the intent-to-treat (ITT) population and subgroups based on programmed death ligand-1 (PD-L1) expression.
• To assess the role of PD-L1 as a potential prognostic biomarker in advanced GC/GEJC.

Main Methods:

• Phase 3, randomized, double-blind, placebo-controlled trial (RATIONALE-305) enrolling 997 patients with advanced GC/GEJC.
• Patients received either tislelizumab + chemotherapy or placebo + chemotherapy.
• Primary endpoints included overall survival (OS) and progression-free survival (PFS) in the ITT population and PD-L1 positive subgroups (Tumor Area Positivity score ≥5%).

Main Results:

• Tislelizumab + chemotherapy significantly improved OS (15.0 vs. 12.9 months; HR 0.79) and PFS (6.9 vs. 6.2 months; HR 0.79) in the ITT population.
• Similar OS and PFS benefits were observed in patients with PD-L1 TAP score ≥5% (OS: 16.4 vs. 12.8 months; PFS: 7.2 vs. 5.9 months).
• No new safety signals were identified after 3 years of follow-up, indicating a favorable safety profile.

Conclusions:

• Tislelizumab plus chemotherapy demonstrates durable and improved efficacy outcomes in advanced GC/GEJC at 3 years.
• The combination therapy supports its role as a valuable first-line treatment option.
• PD-L1 expression (TAP score ≥5%) may serve as a potential prognostic biomarker for treatment response.