Impact of Bevacizumab Relative Dose Intensity and Treatment-Induced Proteinuria on the Efficacy of Trifluridine/Tipiracil Plus Bevacizumab in Metastatic Colorectal Cancer.

Background: Trifluridine/tipiracil (FTD/TPI) combined with bevacizumab (Bev) is an established later-line therapy for metastatic colorectal cancer (mCRC). However, the clinical impact of insufficient Bev dose intensity, often caused by cumulative renal toxicity, on treatment efficacy remains unclear. Methods: This retrospective cohort study evaluated 101 patients with mCRC receiving FTD/TPI + Bev to determine the clinical impact of Bev relative dose intensity (RDI). Based on a receiver-operating-characteristic analysis, a Bev RDI cutoff of 70% was established, categorizing patients into high-RDI (≥70%, n = 75) and low-RDI (<70%, n = 26) groups. Results: The high-RDI group demonstrated significantly longer progression-free survival (131 vs. 82 days, p = 0.003) compared to the low-RDI group. For overall survival, although statistical significance was not reached, a favorable trend was observed in the high-RDI group (343 vs. 215 days, p = 0.093). The disease control rate was also significantly higher in the high-RDI group (46.7% vs. 23.1%, p = 0.040). Treatment interruption due to proteinuria was the primary cause of reduced RDI. Furthermore, a history of severe proteinuria during prior anti-VEGF therapy strongly predicted its recurrence during the current regimen. Conclusions: Maintaining the dose intensity of Bev is crucial for maximizing the efficacy of FTD/TPI + Bev, highlighting the necessity of long-term proteinuria management across treatment lines.