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 brief
Tislelizumab plus chemotherapy cut progression or death risk 35% to 45%
In 475 patients with advanced gastric or gastroesophageal junction cancer and a PD-L1 score of at least 5%, tislelizumab plus chemotherapy was linked to 35% to 45% lower risk of progression or death and 27% to 35% lower risk of death across patient-reported domains. Worsening quality of life, pain, and dietary restrictions predicted progression, but the model shows associations, not that symptom changes cause survival differences.
- Journal
- Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation (Q1)
- Published
- 25 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Markus Moehler, Marcia Cruz Correa, Do Youn Oh, Rui-Hua Xu, Ken Kato, Afsaneh Barzi, et al.
- PMID
- 42927580
- DOI
- 10.1007/s11136-026-04416-4
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 1 November 2026): PROs prognostic for progression and survival
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PROs have significant prognostic value for disease progression and survival in patients with PD-L1 TAP score ≥ 5%. REGISTRATION NUMBER: NCT03777657 ( http://clinicaltrials.gov ).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.