For a study, the researchers sought to compare the effects of tislelizumab, a programmed cell death protein 1 inhibitor, combined with chemotherapy to chemotherapy alone as the first-line treatment in patients with advanced nonsquamous non–small cell lung cancer (nSQ-NSCLC). Patients with histologically proven stage IIIB/IV nSQ-NSCLC were randomised 2:1 to tislelizumab plus platinum-pemetrexed (arm T + PP) or platinum-pemetrexed alone (arm PP) in the randomised, open-label, multicenter phase III trial RATIONALE 304 (NCT03663205). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questions and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Lung Cancer were used to assess health-related QoL. Mean score change from baseline in the 30-item Quality of Life Questionnaire Core’s global health status/quality of life (GHS/QoL) at weeks 12 (during chemotherapy) and 18 (after chemotherapy) were key patient-reported outcomes endpoints, as was time to deterioration in GHS/QoL. A total of 332 patients received at least 1 dosage of the study medication and completed at least 1 HRQoL evaluation. At week 18, the T + PP arm’s global health status/QoL score improved (between-group least square mean difference, 5.7; 95% confidence interval [CI], 1.0–10.5; P=0.018). Coughing (−5.9; 95% CI, 11.6 to 0.1; P=0.044), dyspnea (−3.8; 95% CI, 7.8 to 0.1; P=0.059), chest discomfort (−6.2; 95% CI, 10.8 to 1.6; P=0.008), and peripheral neuropathy (−2.6; 95% CI, 5.5 to 0.2; P=0.066) were all reduced in patients in arm T + PP. The median time to worsening in GHS/QoL was attained in neither arm. The addition of tislelizumab to platinum-based chemotherapy improved HRQoL and the key disease-specific symptoms of coughing, chest discomfort, and dyspnea in nSQ-NSCLC patients.