Residual Platinum-Induced Neuropathy and the Feasibility of Second-Line Paclitaxel-Ramucirumab Therapy in Advanced Gastric Cancer: Prospective Multicenter Evidence from Japan.

backgroundPlatinum-based doublets are standard first-line therapy for advanced gastric cancer (GC) in the Western Pacific region, but oxaliplatin frequently induces persistent peripheral sensory neuropathy (PSN). Whether residual PSN compromises the feasibility and efficacy of subsequent paclitaxel (PTX)-based therapy remains unclear.

methodsThe IVY study was a prospective, multicenter observational trial conducted across 16 Japanese institutions. Patients with advanced GC progressing after fluoropyrimidine-platinum therapy received second-line PTX ± ramucirumab. Baseline PSN was assessed by CTCAE, PNQ, and FACT/GOG-Ntx. The primary endpoint was the incidence of grade ≥ 3 PSN during second-line therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), tumor response, and patient-reported outcomes.

resultsAmong 156 patients (90 PSN-positive, 66 PSN-negative), grade ≥ 3 PSN occurred more frequently in the PSN-positive group (16.7% vs. 4.5%;

conclusionsResidual PSN increases the risk of clinically relevant neurotoxicity-particularly in patients with baseline grade ≥ 2-but, in this cohort, did not appear to preclude paclitaxel-based second-line therapy when monitoring and dose modification were available. The apparent survival difference was exploratory and, after adjustment for baseline imbalance, should not be interpreted as a benefit attributable to residual PSN. Residual neuropathy should therefore prompt structured baseline assessment and early-cycle monitoring rather than routine reassurance.