Quality-adjusted survival comparison for tislelizumab (TIS) + chemotherapy (CT) versus placebo (PBO) + CT as first-line (1L) treatment in gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) patients with peritoneal metastasis (PM): Long-term follow-up from RATIONALE-305.

Abstract

4034 Background: There is an unmet need for better treatment among patients (pts) with PM. A post hoc analysis of the phase 3 RATIONALE-305 (NCT03777657) trial showed that TIS + CT as 1L treatment for GC/GEJC pts with PM improved survival compared to PBO + CT (Qiu et al, 2025). The current study evaluated whether this survival benefit translated into quality of life (QoL) adjusted survival gains. Methods: This post hoc analysis used long-term follow-up data from the RATIONALE-305 trial (minimum follow-up 3 years; data cutoff February 28, 2024). The analysis focused on the intent-to-treat (ITT) population and subgroups defined by programmed death ligand-1 (PD-L1) ≥1% as well as ≥5% by Tumor Area Positivity (TAP) score. The well-established Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) methodology was used. QoL adjusted survival was calculated as the average time spent in three distinct health states during the trial follow-up: survival time with grade 3/4 toxicity, survival without progression/toxicity, and survival post progression, each weighted by QoL utility parameters specific to that state. A sensitivity analysis (SA) using trial-derived, treatment-specific EQ-5D utility values was also conducted. QoL adjusted relative survival gains ≥15% were considered “clearly clinically important,” in line with commonly accepted Q-TWiST benchmarks (DOI 10.1007/s11136-005-1579-7). Results: At the maximum follow-up of 57 months in all randomized pts in RATIONALE-305, TIS + CT (n=501) pts experienced greater mean QoL adjusted survival than PBO + CT (n=496) (16.3 vs 13.1 months). Among pts with PM, TIS + CT (n=220) showed higher mean QoL adjusted overall survival than PBO + CT (n=214) (13.4 vs 10.8 months; 17.7% relative Q-TWiST gain) that was clearly clinically important. QoL adjusted survival benefit was also clearly clinically important in TIS + CT pts with PM with PD-L1 TAP score ≥1% (16.8% gain) and PD-L1 score ≥5% (33.0% gain) compared with PBO + CT. SA results further favored TIS + CT (Table). Conclusions: Treatment with TIS + CT resulted in clinically meaningful improvement in long-term quality-adjusted survival for GC/GEJC pts with PM versus those receiving CT alone. Clinical trial information: NCT03777657 . TIS + CT vs PBO + CT treatment difference. Mean Q-TWiST, months (95% CI) Relative Q-TWiST Gain Pts with PM a ITT pts (n=434) 2.6 (0.1 to 5.0), P =0.04 17.7% PD-L1 TAP ≥1% (n=386) 2.5 (0.1 to 5.1), P <0.05 16.8% PD-L1 TAP ≥5% (n=217) 4.7 (1.1 to 8.6), P =0.02 33.0% Pts with PM (SA using EQ-5D scores) b ITT pts (n=434) 3.1 (0.8 to 5.5), P <0.01 21.3% PD-L1 TAP ≥1% (n=386) 3.1 (0.5 to 5.6), P =0.02 20.8% PD-L1 TAP ≥5% (n=217) 4.8 (1.3 to 8.2), P <0.01 33.9% a Using standardized base case Q-TWiST utility weights. b Using US mapping algorithm weights.