Purpose: Trifluridine/tipiracil (FTD/TPI) improves the overall survival (OS) of metastatic colorectal cancer (mCRC) patients. Additionally, FTD/TPI plus bevacizumab (BEV) has demonstrated promising efficacy for mCRC patients who are refractory to standard chemotherapy. Chemotherapy-induced neutropenia (CIN) has been reported to be an indicator of efficacy for FTD/TPI. This study investigated whether CIN was an indicator of efficacy for FTD/TPI plus BEV.
Methods: We reviewed chemo-refractory mCRC patients who were treated with FTD/TPI alone (monotherapy) or FTD/TPI plus BEV (combination) at our institution and compared the safety and efficacy of the two. Progression-free survival (PFS) and OS were analyzed using Kaplan-Meier curves. We also investigated correlations between CIN and outcomes.
Results: In total, 56 patients received FTD/TPI, among whom 24 and 32 were treated with monotherapy and combination therapy, respectively. The median PFS was 1.8 and 4.7 months for the monotherapy and combination arms, respectively (hazard ratio [HR]: 0.28; 95% confidence interval [CI]: 0.15-0.51; P < 0.001). The median OS was 6.3 and 11.7 months for the monotherapy and combination arms, respectively (HR 0.25; 95% CI 0.13-0.48; P < 0.001). CIN (Grade 3 or worse) developed in five (20.8%) and 17 (53.1%) patients from the monotherapy and combination arms, respectively (P = 0.030). Patients with CIN in the combination arm had improved PFS and OS compared with non-CIN patients (P = 0.033 and P = 0.045, respectively).
Conclusions: FTD/TPI plus BEV prolonged PFS and OS and had tolerable toxicity compared with FTD/TPI alone. CIN is an indicator of patients who will benefit from FTD/TPI plus BEV.
Keywords: Chemotherapy; FTD/TPI plus bevacizumab; Metastatic colorectal cancer; Neutropenia.