First-Line Tislelizumab Plus Chemotherapy for Advanced or Metastatic Squamous Non-Small Cell Lung Cancer: 4-Year Long-Term Follow-Up from RATIONALE-307

INTRODUCTION: Squamous nonsmall cell lung cancer (sq-NSCLC) is challenging to treat, with shorter survival when compared with other NSCLC subtypes. Tislelizumab has demonstrated efficacy when combined with chemotherapy for sq-NSCLC. We report 4-year follow-up results from the phase 3 randomized RATIONALE-307 trial evaluating tislelizumab plus chemotherapy as first-line treatment for advanced or metastatic sq-NSCLC. METHODS: Patients with treatment-naive advanced or metastatic sq-NSCLC were randomized to receive tislelizumab plus paclitaxel/carboplatin (arm A), tislelizumab plus nab-paclitaxel/carboplatin (arm B), or paclitaxel/carboplatin alone (arm C) until disease progression/intolerable toxicity. Crossover was permitted from arm C to tislelizumab monotherapy. The primary end point was progression-free survival (PFS) per independent review. Key secondary end points included overall survival (OS) and safety. RESULTS: At median OS follow-up of 44.8 months, tislelizumab plus chemotherapy demonstrated durable survival benefit. Median PFS was 7.7 months (95% confidence interval [CI] 6.7-9.9) in arm A, 9.5 months (95% CI 7.4-10.1) in arm B, and 5.5 months (95% CI 4.2-5.6) in arm C. Median OS was 26.1 months (95% CI 19.0-33.8) in arm A, 23.3 months (95% CI 18.8-26.4) in arm B, and 19.4 months (95% CI 16.0-23.4) in arm C. The 4-year OS rates were 32.2%, 26.0%, and 19.2% for arms A, B, and C, respectively. Crossover occurred in 58.7% of patients from arm C. OS and PFS benefits were observed across most subgroups. Grade ≥ 3 treatment-emergent adverse events occurred in 89.2%, 89.0%, and 84.6% of patients in arms A, B, and C, respectively. No new safety signals emerged. CONCLUSIONS: At 4-year follow-up, patients with advanced sq-NSCLC who received tislelizumab plus chemotherapy experienced long-term OS and PFS benefits versus chemotherapy alone, despite high crossover rates. The combination was well-tolerated with no new safety concerns. This regimen may be a promising first-line treatment option for patients with advanced or metastatic sq-NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03594747.