Prognostic associations between patient-reported outcomes and progression-free and overall survival in advanced gastric or gastroesophageal junction adenocarcinoma with PD-L1 TAP score ≥ 5%: results from the RATIONALE-305 trial

In RATIONALE-305, tislelizumab plus chemotherapy improved overall survival (OS) versus placebo plus chemotherapy in advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) with programmed death-ligand 1 (PD-L1) tumor area positivity (TAP) score ≥ 5% and in all patients. Here, we present a three-component joint model (JM) developed to evaluate associations between patient-reported outcomes (PROs) and risk of progression-free survival (PFS) and OS events. Longitudinal PRO data were analyzed using the EORTC QLQ-C30 and QLQ-STO22. The JM linked: (1) a linear mixed model (LMM) for change from baseline in PRO scores; (2) a Cox model for time to recurrent symptomatic deterioration (RS-D); and (3) a Cox model to evaluate the RS-D event frailty prediction of PFS and OS. 475 patients in the PD-L1 ≥ 5% subgroup (tislelizumab + chemotherapy, n = 238; placebo + chemotherapy, n = 237) were evaluated. In PFS and OS LMMs, tislelizumab + chemotherapy versus placebo + chemotherapy was associated with improved GHS/QoL (global health status/quality of life) (p = 0.01) and reduced dietary restrictions (p = 0.05). In the OS LMM, tislelizumab + chemotherapy was associated with reduced upper GI symptoms (p = 0.01) and reductions in dietary restrictions (p = 0.02). RS-D in GHS/QoL, pain, and dietary restrictions were leading predictors of PFS risk. Across all QLQ-C30 and QLQ-STO22 domains, tislelizumab plus chemotherapy significantly reduced the risk of progression or death (PFS HRs 0.55–0.65; 35–45% reduction) and death (OS HRs 0.65–0.73; 27–35% reduction); all p ≤ 0.01. PROs have significant prognostic value for disease progression and survival in patients with PD-L1 TAP score ≥ 5%. NCT03777657 ( http://clinicaltrials.gov ). Stomach and gastroesophageal junction cancers are among the most common and deadly cancers worldwide, and patients often suffer significant symptoms that reduce their quality of life. While patient-reported outcomes (i.e., surveys where patients describe their own symptoms and wellbeing) are known to matter in cancer care, it has been unclear how changes in these reports over time relate to disease progression and survival. This study linked patients’ ongoing symptom reports with their clinical outcomes in a large clinical trial of the immunotherapy tislelizumab combined with chemotherapy. The results demonstrated that worsening health-related quality of life, pain, and dietary difficulties were early warning signs of disease progression or death, while treatment with tislelizumab consistently protected against both. These findings support using patient-reported disease-specific symptoms as meaningful clinical tools to guide treatment decisions and improve care for patients with advanced gastric cancer.