Trifluridine–tipiracil plus bevacizumab versus trifluridine–tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis

Abstract

Abstract Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included − 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42–0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52–0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51–6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28–2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19–1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44–0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR. Graphical Abstract

Keywords

• Colorectal cancer
• Trifluridine-tipiracil
• Bevacizumab
• anti-VEGF antibody