Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage small-cell lung cancer: patient-reported outcomes in the RATIONALE-312 trial.

OBJECTIVE

In the phase 3 RATIONALE-312 trial (ClinicalTrials.gov Identifier: NCT04005716), the addition of tislelizumab to chemotherapy as first-line treatment significantly improved overall survival and progression-free survival compared to placebo plus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), with an acceptable safety profile. This analysis reports the patient-reported outcomes (PROs) from RATIONALE-312.

METHODS

Overall, 457 adults with ES-SCLC were randomized (1:1) to tislelizumab plus chemotherapy (n = 227) or placebo plus chemotherapy (n = 230). PROs were protocol-prespecified secondary end points that assessed health-related quality of life (HRQoL) using the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires. PRO end points at Cycles 4 and 6 were analyzed using a mixed model for repeated measures. Time to deterioration (TTD) was evaluated.

RESULTS

At Cycle 4, the tislelizumab arm demonstrated clinically meaningful improvement in coughing, hemoptysis, and chest pain. Clinically meaningful improvement was observed in the tislelizumab arm, but not in the placebo arm, for global health status (GHS)/QoL, dyspnea, and arm or shoulder pain. By Cycle 6, the tislelizumab arm achieved clinically meaningful improvement in GHS/QoL, with a statistically significant between-group difference favoring the tislelizumab arm. Clinically meaningful improvements in dyspnea, coughing, hemoptysis, and chest pain were maintained in the tislelizumab arm through Cycle 6. No between-group differences were observed in the TTD analysis.

CONCLUSIONS

Tislelizumab plus chemotherapy maintained or improved HRQoL and patient-reported symptoms compared to placebo plus chemotherapy. Along with prior efficacy and safety data, these data support tislelizumab plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.