Efficacy and safety of trifluridine/tipiracil plus ramucirumab in advanced gastric cancer as third-line or later treatment: A multicenter phase II study.

367 Background: Later-line treatment options for advanced gastric cancer (AGC), including nivolumab, irinotecan, and trifluridine/tipiracil (FTD/TPI), provide limited clinical benefit. Recent studies suggest that FTD/TPI with ramucirumab (Ram) may improve outcomes, but prospective data in clinical practice is insufficient. Methods: This multicenter, prospective, single-arm, phase II trial evaluated FTD/TPI plus Ram as third-line or later therapy in unresectable or recurrent AGC. Eligible patients had prior fluoropyrimidine-, platinum-, and Ram-containing regimens. FTD/TPI (35 mg/m²) was administered orally twice daily on days 1–5 and 8–12, and Ram (8 mg/kg) intravenously on days 1 and 15, every 28 days. The primary endpoint was time to treatment failure (TTF); secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), relative dose intensity (RDI), and safety. Results: Between February 2022 and March 2024, 32 patients were enrolled (median age, 72.5 years; 53.1% male). Ram was reintroduced as a rechallenge in 18 patients (56.3%) and continued from the prior therapy in 14 (43.8%). The median TTF was 4.0 months (95% CI, 2.8–5.0), meeting the primary endpoint. Median PFS and OS were 4.8 months (95% CI, 2.8–8.3) and 12.2 months (95% CI, 7.8–17.2), respectively. Among 26 patients with measurable lesions, ORR was 11.5% and DCR was 76.9%. The mean RDI was 78.6% for FTD/TPI and 93.1% for Ram. Post-discontinuation therapy was given to 17 patients (53.1%). Grade ≥3 neutropenia occurred in 17 patients (53.1%), and febrile neutropenia in 3 (9.4%). Common non-hematologic adverse events were anorexia (68.8%), fatigue (59.4%), and proteinuria (59.4%), mostly grade 1–2. Dose modification to a biweekly FTD/TPI schedule was implemented in 15 patients at the physician’s discretion for grade ≥3 neutropenia or other adverse events. Grade ≥3 neutropenia occurred in 10 of 50 cycles (20%) under this schedule, with no febrile neutropenia observed. Conclusions: FTD/TPI plus ramucirumab demonstrated promising efficacy and manageable toxicity as third-line or later therapy for unresectable or recurrent AGC. These findings warrant further investigation in larger, randomized studies to confirm the clinical benefits. Clinical trial information: jRCTs041210105 .