Results of a multicenter retrospective cohort study evaluating the safety and efficacy of FTD/TPI plus ramucirumab in advanced gastric cancer (HGCSG2302).

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Background: In advanced gastric cancer, trifluridine/tipiracil (FTD/TPI) is one of the standard treatments for later-line chemotherapy. Ramucirumab (RAM), an anti-VEGFR-2 monoclonal antibody, has shown promising efficacy in combination with FTD/TPI in phase II studies conducted in Japan, suggesting that this combination could improve treatment outcomes. However, there remains a paucity of real-world clinical data comparing the efficacy and safety of FTD/TPI monotherapy and FTD/TPI plus RAM combination therapy in general clinical practice. Methods: This retrospective analysis to evaluate safety and efficacy included patients with gastric cancer who were received FTD/TPI plus RAM combination therapy or FTD/TPI monotherapy between August 2019 and March 2023 at 21 institutions. Results: 164 patients were analyzed, 38 patients in the RAM combination group and 126 in the FTD/TPI monotherapy group. The distribution of treatment lines (third/fourth/fifth) was 10/13/15 in the RAM group and 26/54/46 in the monotherapy group, respectively. RAM had been previously administered to 34 patients (89.5%) in the RAM group. Objective response rate and disease control rate were 11.1% / 55.6% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the RAM group and 5.5% /38.5% (OR 2.0, 95% C.I. 0.84-4.77, p=0.126) in the monotherapy group, respectively. Median progression-free survival (PFS) was 3.5 months in the RAM group and 2.1 months in the monotherapy group (HR 0.69, 95% C.I. 0.49-1.02, p=0.06), respectively. Median overall survival (OS) was 8.4 months in the RAM group and 5.8 months in the monotherapy group (HR 0.82, 95% C.I. 0.54-1.25, p=0.350), respectively. Grade 3 neutropenia was reported in 48.6%/52.4% (p=0.707), and there were no significant differences in other adverse event profiles between the two groups. Additionally, in the RAM group, a comparison between patients receiving standard dosing (2 weeks on/2 weeks off; n=7) and those on biweekly dosing (1 week on/1 week off; n=24) showed no notable differences in efficacy or safety. Conclusions: FTD/TPI plus RAM combination therapy showed a trend toward prolonged PFS compared to FTD/TPI monotherapy, but no significant difference in OS.