PRO-based deterioration predicts survival in PD-L1 ≥5% advanced gastric cancer: RATIONALE-305 results

Prof Eric van Cutsem and Prof Markus Möhler discussed recent findings from the RATIONALE 305 trial, a phase 3 study evaluating the efficacy of chemotherapy with or without tislelizumab in advanced gastric and gastroesophageal junction adenocarcinoma. The trial demonstrated a notable survival benefit with the combination therapy. Specifically, the median OS exceeded 17 months, with approximately 40% of patients alive at two years, suggesting a meaningful improvement over historical outcomes for this patient population.

The discussion emphasised the importance of identifying predictive biomarkers for long-term benefit. In this context, PROs are gaining relevance. Recent data presented at the ESMO GI congress highlight, for the first time, a potential predictive value of PROs in patients receiving tislelizumab. Worsening scores in parameters such as fatigue, nausea, vomiting, and physical functioning—assessed across two or more time points—were associated with poorer clinical outcomes. These findings imply that regular monitoring of PROs can identify patients at risk for disease progression or functional decline. Early supportive interventions, including nutritional support, physical activity programs, and symptom-directed therapies, may be warranted in such cases to maintain quality of life and potentially improve outcomes.

A further aspect of the RATIONALE 305 study involves the evaluation of tumor PD-L1 expression using the TAP score, compared to the more established CPS. The TAP score quantifies PD-L1 expression by measuring the area of positivity, rather than individual cell counts as used in CPS. Recent comparative analyses indicate high concordance between the two scoring systems. TAP has the added advantage of being more amenable to AI-based image analysis, which could facilitate faster and more reproducible assessment. 

Prof Möhler emphasised the importance of broadening regulatory frameworks to accommodate PD-L1 positivity determined by different validated scoring systems. In Germany, many pathologists are already applying both TAP and CPS in parallel, showing increasing adoption of the TAP method. These developments underscore the clinical activity of tislelizumab in gastric cancer and the need to optimise biomarker strategies to enhance patient selection and streamline diagnostic workflows.