RATIONALE-303: Long-Term Outcomes of Tislelizumab in Previously Treated Advanced/Metastatic NSCLC

Introduction: RATIONALE-303 (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. We present long-term outcomes with an additional 30-month follow-up after the final analysis. Methods: In this open-label, randomized, phase 3 trial, patients aged 18 years or older with locally advanced or metastatic NSCLC that progressed on prior platinum-based chemotherapy were randomized (2:1) to tislelizumab or docetaxel. The dual primary end points were overall survival (OS) in the intent-to-treat (ITT) population and OS in patients with programmed death-ligand 1 (PD-L1) tumor cell expression 25% or greater. Secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results: = 115). At the data cutoff (January 18, 2024), the median OS follow-up was 46.5 months (tislelizumab) and 41.0 months (docetaxel). The median OS was 16.9 versus 11.9 months (stratified hazard ratio [HR] = 0.67; 95% confidence interval [CI]: 0.57-0.80) and 19.3 versus 11.5 months (stratified HR = 0.52; 95% CI: 0.40-0.68) for tislelizumab versus docetaxel in the ITT and PD-L1 25% or greater populations, respectively. In the ITT population, tislelizumab showed improved PFS (median 4.2 versus 2.6 mo; HR = 0.64; 95% CI: 0.54-0.76), a higher ORR (22.6% versus 7.8%), and a longer DoR (median 13.5 versus 6.1 mo) than docetaxel. Grade 3 or higher treatment-related adverse events were less frequent with tislelizumab than with docetaxel (16.1% versus 66.3%). No new safety signals were identified. Conclusions: Extended follow-up confirmed clinically meaningful improvements in OS and other efficacy outcomes with tislelizumab versus docetaxel in previously treated advanced/metastatic NSCLC, with a favorable safety profile. Clinical trial registration: NCT03358875.