Effect of pretreatment vascular endothelial growth factor inhibitor use on the safety and efficacy of trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer.

BACKGROUND: The effect of vascular endothelial growth factor (VEGF) inhibitor pretreatment on clinical outcomes of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients with metastatic colorectal cancer (mCRC) remains unclear. We aimed to investigate this effect.

METHODS: Patients with mCRC treated with FTD/TPI plus BEV were retrospectively enrolled. Disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. In total, 73, 50, and 33 patients were treated with fluorouracil+levofolinate calcium+irinotecan (FOLFIRI) plus BEV, ramucirumab, and aflibercept, respectively.

RESULTS: The DCR and median PFS/OS did not significantly differ among the groups (DCR: 54.8% vs. 56.0% vs. 42.4%, P = 0.43; PFS: 3.9 vs. 4.6 vs. 3.7 months, P = 0.45; OS: 12.0 vs. 9.5 vs. 11.9 months, P = 0.28). The most common grade 3-4 AE was neutropenia. The incidence of grade 3-4 AEs did not significantly differ among the groups. The frequency of grade ≥2 proteinuria during FTD/TPI plus BEV treatment was significantly higher in patients with grade ≥2 proteinuria before FOLFIRI plus VEGF inhibitor use than in those without proteinuria. Multivariate analysis revealed poor performance status (ECOG PS) and liver metastasis as independent predictors of short PFS/OS (ECOG PS, PFS: P = 0.021, OS: P < 0.001; liver metastasis, PFS: P = 0.03, OS: P < 0.001) and grade 3-4 neutropenia in a month as a predictor of long PFS/OS (PFS: P = 0.047, OS: P = 0.03).

CONCLUSION: Different pretreatment VEGF inhibitors did not affect the efficacy and safety of FTD/TPI plus BEV.