Early Safety Outcomes of Biweekly Versus Conventional FTD/TPI Plus Bevacizumab in Colorectal Cancer: PRABITAS Analysis
[Background]
PRABITAS is a pragmatic, randomized phase III trial comparing biweekly versus conventional trifluridine/tipiracil (FTD/TPI) + bevacizumab (BEV) in metastatic colorectal cancer. The pragmatic design minimizes eligibility restrictions and permits physician-directed initiation and dose modifications. This first report from PRABITAS focuses on early treatment-related adverse event (TRAE) profiles.
[Methods]
Baseline characteristics and TRAEs were assessed in patients treated with conventional FTD/TPI + BEV (Arm A: FTD/TPI on day 1-5 and 8-12 every 28 days) or biweekly FTD/TPI + BEV (Arm B: FTD/TPI on day 1-5 every 14 days). Eligibility was assessed based on typical explanatory trial criteria, and patients were categorized as eligible or ineligible. Safety analyses included Cycles 1-2 in Arm A and Cycles 1-4 in Arm B, with events graded by CTCAE v5.0.
[Results]
A total of 972 patients from 179 institutions were enrolled from December 2023 to May 2025. Baseline characteristics and initial FTD/TPI dose reductions were balanced. Overall, 15.3% were ineligible under the explanatory trial criteria, most commonly due to ECOG PS 2, organ dysfunction or comorbidities. Compared with Arm A, Arm B showed lower rates of grade ≥2 nausea (14.2% vs. 8.0%), diarrhea (7.0% vs. 1.7%), fatigue (19.7% vs. 10.9%), and grade ≥3 neutropenia (39.2% vs. 13.6%). Febrile neutro
