Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: patient-reported outcomes in the RATIONALE-305 study

RATIONALE-305 (NCT03777657) demonstrated that tislelizumab plus chemotherapy statistically improved overall survival versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). This analysis examined patient-reported outcomes (PROs) at final analysis. Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized (1:1) to tislelizumab or placebo intravenously once every 3 weeks plus chemotherapy. PROs assessed health-related quality of life (HRQoL) using EORTC QLQ-C30 and EORTC QLQ-STO22. A mixed model for repeated measures was used for PRO endpoints at treatment cycles 4 and 6, and time to deterioration was analyzed. Tislelizumab arm had improved outcomes over placebo arm in least-squares (LS) mean change from baseline to cycle 6 for QLQ-C30 global health status/quality of life (GHS/QoL) (LS mean difference, 2.52 [95% CI: 0.29–4.74]), physical functioning (2.46 [0.49–4.43]), fatigue (–3.01 [–5.78 to −0.24]), and STO22 index score (–1.62 [–3.12 to −0.12]) as well as maintenance of upper gastrointestinal symptoms (–1.74 [–3.55–0.06]) and pain/discomfort (–1.88 [–4.03–0.27]). Patients receiving tislelizumab plus chemotherapy had a lower risk for deterioration of GHS/QoL (hazard ratio 0.77 [95% CI: 0.60–0.98]), physical functioning (0.72 [0.57–0.92]), STO22 index score (0.64 [0.45–0.92]), pain/discomfort (0.74 [0.58–0.96]), and upper gastrointestinal symptoms (0.73 [0.56–0.95]). Advanced GC/GEJC patients treated with tislelizumab plus chemotherapy versus placebo plus chemotherapy in first-line had sustained and improved HRQoL. These results, along with previous efficacy and safety data, support tislelizumab plus chemotherapy as a first-line treatment option for GC/GEJC. The RATIONALE-305 trial is registered on ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT03777657).ClinicalTrials.gov identifier: NCT03777657.