Multicenter phase 3 trial of first-line perioperative tislelizumab plus neoadjuvant chemotherapy for resectable non-small cell lung cancer

The phase 3 RATIONALE-315 trial, at 50 centers in China, evaluated addition of perioperative tislelizumab to neoadjuvant platinum-based doublet chemotherapy for resectable stage II-IIIA non-small cell lung cancer. Patients with previously untreated disease were randomized to neoadjuvant tislelizumab (n=226) or placebo (n=227) plus neoadjuvant chemotherapy, followed by surgery and adjuvant tislelizumab or placebo. Major pathological response rate (MPR) was 56% in the tislelizumab group versus 15% in the placebo group (p<0.001). Median event-free survival (EFS) was not reached in either group but was significantly improved with tislelizumab compared to placebo (HR 0.56; p=0.0003). Grade 3 or worse adverse events were seen in 72% versus 66%, and serious treatment-related adverse events in 15% versus 8%. Fourteen percent of patients in the tislelizumab group and 20% of patients in the placebo group died during the study. The authors conclude that addition of perioperative tislelizumab to neoadjuvant chemotherapy was associated with significantly improved MPR and EFS among patients with resectable stage II-IIIA NSCLC, with a manageable safety profile.