Global health status time to deterioration after systemic treatments of advanced gastric cancer: a systematic review and trial-level analysis

Objective: Although health-related quality of life (HRQoL) endpoints have often demonstrated a benefit from treatments that have prolonged overall survival (OS), their relationship with OS and other clinical trial endpoints remains unclear. The study aims to conduct a systematic review of phase III trials assessing HRQoL, time-to-deterioration (TTD), and imaging-related endpoints in patients with advanced gastric cancer receiving systemic therapy. Methods: A systematic review identified phase III trials reporting results of OS, TTD and imaging-related endpoints, such as progression-free survival (PFS) and objective response rate (ORR). From each trial the results of the four endpoints were extracted. An arm-level and a trial-level analysis were carried out. Results: Sixteen articles were identified, reporting the results of HRQoL endpoint of 17 trials. From the trials complete data of 21 study arms and 15 trial-level comparisons were available. At the arm-level analysis, all the endpoints reported a significant correlation with OS. The trial-level analysis documented a consistent relationship of treatment effects between PFS and OS (R2=0.313; β = 0.174; p-value = 0.030), but not between ORR and OS and between TTD and OS. Conclusion: None of the endpoints examined can be considered a surrogate for OS, although PFS remains the variable that correlates most closely with OS in the trial-level analysis. The TTD of the EORTC-QLQ-C30 GHS subscale requires standardization and subsequent prospective and retrospective re-evaluation as a surrogate endpoint. However, it warrants greater attention in future studies as a co-primary or secondary outcome, as it could provide additional and clinically relevant information compared with imaging-related outcomes.