The efficacy and safety of trifluridine/tipiracil plus bevacizumab compared with trifluridine/tipiracil monotherapy for metastatic colorectal cancer: A meta-analysis

Background: Some small sample size studies have yielded slightly inconsistent results for comparing the efficacy and toxicity of trifluridine/tipiracil (TAS-102) with or without bevacizumab. This meta-analysis aims to further investigate the additive effect and safety profile of bevacizumab when combined with TAS-102 in patients receiving a salvage-line treatment for metastatic colorectal cancer (mCRC). Methods: A systematic literature search was conducted using PubMed, Web of Science, Cochrane Library, and some oncological conferences by the end of February 2021. No restrictions were placed on the searches. Two reviewers independently performed the retrieval and selection according to the “Patient, Intervention, Comparison, Outcome, Study design” principle. The outcome endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs). Results: Six controlled trials which recruited 435 refractory mCRC patients were ultimately taken in. Our results suggested that the regimen of TAS-102 plus bevacizumab had a significant advantage in OS, PFS, and DCR over TAS-102 alone (hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.27–0.67, P < 0.001; HR = 0.48, 95% CI: 0.39–0.59, P < 0.001; OR = 3.19, 95% CI: 1.56–6.50, P = 0.001; respectively). In general, the incidence of AEs was slightly but not obviously higher in the combination therapy group than the monotherapy group (OR = 1.08; 95% CI: 0.89–1.30; P = 0.458). However, the most frequent grade 3 or worse AE was neutropenia (OR = 2.32; 95% CI: 1.53–3.52; P < 0.001) which was higher in the TAS-102 plus bevacizumab group. Meanwhile, the morbidity of anemia (OR = 0.43; 95% CI: 0.22–0.83; P = 0.013) was significantly higher in TAS-102 monotherapy group. Conclusion: TAS-102 plus bevacizumab has promising activity with a manageable safety profile in a salvage-line treatment for mCRC who are refractory or intolerant to standard chemotherapy.