DOI: 10.6084/m9.figshare.31210867.v1
title: 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

description: 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. Overall, 457 adults with ES-SCLC were randomized (1:1) to tislelizumab plus chemotherapy (<i>n</i> = 227) or placebo plus chemotherapy (<i>n</i> = 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. 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. 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. Small-cell lung cancer is a fast-growing cancer that often causes serious symptoms, such as coughing, shortness of breath, chest pain, and fatigue. Because many patients are diagnosed at an advanced stage, treatments should not only help people live longer, but also help them feel better during treatment. The RATIONALE-312 study compared two treatments for people with extensive-stage small-cell lung cancer who had not received treatment before. One group received standard chemotherapy. The other group received chemotherapy plus tislelizumab, a type of immunotherapy that helps the immune system attack cancer cells. Patients in the study regularly completed questionnaires about their quality of life and symptoms. These questionnaires asked how patients felt physically and how much symptoms affected their daily lives. Patients who received tislelizumab with chemotherapy reported improvements in their overall quality of life and in key lung cancer symptoms, including coughing, coughing up blood, chest pain, and shortness of breath. These improvements were seen during treatment and continued after chemotherapy ended. Importantly, adding tislelizumab did not make symptoms worse or cause patients to lose daily functioning sooner. Together with earlier results showing longer survival, these findings suggest that adding tislelizumab to chemotherapy can help patients live longer while also maintaining or improving how they feel during treatment.