First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%:...

Area of Science:

• Oncology
• Immunotherapy
• Gastrointestinal Cancers

Background:

• Tislelizumab plus chemotherapy showed improved overall survival (OS) in HER2-negative gastric/gastroesophageal junction cancer (GC/GEJC).
• Previous analyses focused on PD-L1 Tumor Area Positivity (TAP) scores >= 5% or intent-to-treat populations.
• FDA concerns regarding PD-1 inhibitors for PD-L1 combined positive score < 1 or TAP score < 1% prompted further analysis.

Purpose of the Study:

• To retrospectively analyze the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) in patients with a PD-L1 TAP score >= 1%.
• To evaluate tislelizumab's benefit-risk profile in a specific subgroup of GC/GEJC patients.

Main Methods:

• Retrospective analysis of data from the RATIONALE-305 trial (NCT03777657).
• Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC and PD-L1 TAP score >= 1% were included.
• Patients received either tislelizumab 200 mg or placebo with ICC every 3 weeks.

Main Results:

• Median OS was 15.0 months with tislelizumab plus ICC versus 12.8 months with placebo plus ICC (HR 0.77; 95% CI 0.67-0.90).
• Improvements were observed in progression-free survival, overall response rate, duration of response, and disease control rate.
• OS benefits were sustained at 3-year follow-up, and the safety profile was acceptable with no new signals.

Conclusions:

• Tislelizumab plus ICC is an effective first-line treatment for HER2-negative GC/GEJC patients with PD-L1 TAP score >= 1%.
• The treatment demonstrated a favorable benefit-risk profile in this patient subgroup.