Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non–small cell lung cancer: patient-reported outcomes in the RATIONALE-315 trial

In the phase III RATIONALE-315 trial (NCT04379635), perioperative tislelizumab plus neoadjuvant chemotherapy significantly improved overall and event-free survival versus placebo plus chemotherapy in patients with resectable stage II–IIIA non–small cell lung cancer (NSCLC). Here, report prespecified patient-reported outcomes (PROs). PROs were evaluated using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. A mixed-effects model for repeated measures was used for PRO endpoints at neoadjuvant Cycle 3 and adjuvant Cycles 3, 5, and 7. Time to deterioration (TTD) was also analyzed. 453 patients were randomized to tislelizumab (n = 226) or placebo (n = 227). At adjuvant Cycles 3 and 5, chest pain was maintained with tislelizumab versus worsening with placebo (LSM difference −4.99 [95% CI: −9.06 to −0.93]; p = 0.016) and −4.15 [95% CI: −7.86 to −0.44]; p = 0.028, respectively). At adjuvant Cycle 7, greater improvement in coughing was observed in the tislelizumab arm versus placebo (−5.10 [95% CI: −9.79 to −0.40]; p = 0.034). TTD analysis showed a lower risk of chest pain with tislelizumab (HR 0.58; p = 0.004). Perioperative tislelizumab improved coughing and chest pain compared with placebo in patients with resectable NSCLC. These data provide additional support of this regimen in this patient population. www.clinicaltrials.gov identifier is NCT04379635. Non–small cell lung cancer (NSCLC) is the most prevalent histological subtype of lung cancer, accounting for approximately 85% of all cases. Even when the tumor can be surgically removed, survival outcomes remain poor, and patients frequently experience debilitating symptoms, including coughing, chest pain, and breathlessness that negatively affect their health-related quality of life. Tislelizumab is an anti-PD-1 monoclonal antibody that, when administered alongside platinum-based chemotherapy before surgery (neoadjuvant) and continued after surgery (adjuvant), has demonstrated statistically significant improvements in overall and event-free survival in the phase III RATIONALE-315 trial. This analysis reports the final patient-reported outcomes (PROs) from RATIONALE-315, examining how patients felt throughout perioperative treatment using validated questionnaires assessing global health status, physical functioning, fatigue, coughing, chest pain, and dyspnea. Among 453 randomized patients, those treated with tislelizumab maintained chest pain levels across the adjuvant phase, while placebo-treated patients experienced clinically meaningful worsening. Tislelizumab-treated patients also demonstrated greater improvements in coughing at later adjuvant cycles, with significant between-group differences observed. Time-to-deterioration analyses further confirmed that patients receiving tislelizumab had a significantly lower risk of chest pain worsening compared with placebo. These findings demonstrate that perioperative tislelizumab not only improves survival but also maintains or improves patient-reported lung cancer symptoms, supporting its use in resectable NSCLC.