Pooled analysis of individual patient data (IPD) from clinical trials of trifluridine/tipiracil (FTD/TPI) and bevacizumab (BEV) for metastatic colorectal cancer (mCRC).

152 Background: The combination therapy of FTD/TPI plus BEV showed a survival benefit in the third- or later-line treatment for patients with mCRC. However, it has been reported that the addition of BEV to FTD/TPI increases the incidence of adverse events (AEs), especially hematological AEs. To assess the clinical outcomes of FTD/TPI plus BEV, this pooled analysis was conducted. Methods: IPD for patients who received FTD/TPI plus BEV was collected from 4 clinical trials: C-TASK FORCE, TAS-CC3, TAS-CC4, and BiTS for third- or later-line treatment. This report presents the clinical outcomes of FTD/TPI plus BEV (5 mg/kg in every 2-weeks) in late-line treatment including different schedules for FTD/TPI (standard schedule 70mg/m 2 on days 1-5 and 8-12 in every 4-weeks and biweekly schedule 70mg/m 2 on days 1-5 in every 2-weeks). Efficacy outcomes of different schedules for FTD/TPI were analyzed using IPW with age, ECOG PS, RAS mutation status, primary tumor location, and metastatic site (liver and peritoneal). Results: In the four clinical trials, 145 patients received FTD/TPI plus BEV (57 patients in the standard schedule and 88 patients in the biweekly schedule). The baseline characteristics were as follows: median age, 66 years (65 in the standard group and 67 in the biweekly group); male, 56% (61%/52%); ECOG PS 0, 70% (74%/68%); RAS wild-type, 48% (42%/51%); right-sided tumor, 27% (35%/22%); liver metastasis, 65% (74%/59%); peritoneal metastasis, 15% (7%/19%). The median overall survival time was 11.0 months (11.1 vs. 10.8 months HR 1.27, p = 0.281), the median progression-free survival time was 4.0 months (4.9 vs. 3.9 months HR 1.43, p = 0.062), and disease control rate was 67% (75% vs. 65% OR 0.87, p = 0.201). The most common grade 3/4 adverse events occurring in more than 5% of patients included neutropenia in 32% (58% vs. 16%, p <0.0001), anemia in 9% (12% vs. 7%, p = 0.373), thrombocytopenia in 6% (12% vs. 2%, p = 0.029), and hypertension in 19% (5% vs. 27%, p = 0.0008). Conclusions: The combination therapy of FTD/TPI plus BEV showed promising anti-tumor effects, and the adverse events were tolerable. The biweekly schedule of FTD/TPI was suggested to reduce the risk of hematological AEs without compromising efficacy compared to the standard schedule. Clinical trial information: UMIN000041621 .