Efficacy and Safety of Trifluridine/Tipiracil Plus Ramucirumab in Later-Line Treatment of Advanced Gastric Cancer: A Multicenter, Prospective Phase II Trial
Koki Nakanishi, Mitsuhiro Furuta, Takashi Oshima, Daisuke Kobayashi, Toshifumi Murai, Hirotoshi Noda, Hidenobu Matsushita, Sho Sato, Shizuki Sugita, Kenta Murotani, Yachiyo Kuwatsuka, Chie Tanaka, Yasuhiro Kodera, Mitsuro KandaPURPOSE
Trifluridine/tipiracil (FTD/TPI) plus ramucirumab may improve survival as a later-line therapy for advanced gastric cancer (GC); however, prospective evidence is limited.
PATIENTS AND METHODS
We conducted a multicenter, prospective phase II trial of FTD/TPI plus ramucirumab in patients with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma who had received at least two previous systemic regimens for advanced disease, including a ramucirumab-containing regimen. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Patients received oral FTD/TPI (35 mg/m 2 , days 1-5 and 8-12) and ramucirumab (8 mg/kg, days 1 and 15) every 28 days. The primary end point was time to treatment failure (TTF), and the secondary end points were progression-free survival (PFS), overall survival (OS), response, 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). The median TTF was 4.0 months (95% CI, 2.8 to 5.0), meeting the primary end point. Median PFS and OS were 4.8 (95% CI, 2.8 to 8.3) and 12.2 months (95% CI, 7.8 to 17.2), respectively. Among 26 patients with measurable disease, objective response rate was 11.5%, and DCR was 76.9%. Mean RDI was 78.6% for FTD/TPI and 93.1% for ramucirumab, supporting feasibility in this cohort. Grade ≥3 neutropenia occurred in 53.1% and febrile neutropenia in 9.4%. Frequent nonhematologic events were anorexia (68.8%) and fatigue (59.4%), mostly grade 1 to 2. A modified FTD/TPI schedule was introduced in 15 patients and maintained dose delivery while reducing neutropenia, with no febrile events.
CONCLUSION
FTD/TPI plus ramucirumab met its primary end point and was feasible with manageable safety in heavily pretreated advanced GC. Given the single-arm design, the efficacy findings are hypothesis-generating and warrant confirmation in larger randomized trials.