A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Backgrounds: As a new oral chemotherapy drug, TAS-102 is currently recommended as the third-line treatment for metastatic colorectal cancer (mCRC). Recently, studies have reported the efficacy of TAS-102 combined with bevacizumab in colon cancer patients after standard treatment fails. Here, we evaluated the efficacy and safety of TAS-102 combined with bevacizumab versus TAS-102 as a single agent by a systematic review and a meta-analysis.

Methods: PubMed, Web of Science and Cochrane libraries were searched. Studies involving bevacizumab combined with TAS-102 in mCRC were included. Study characteristics (author, year of publication, country et al.), efficacy (disease control rate(DCR), progression-free survival(PFS), overall survival(OS)) and adverse effects were extract from studies. Forest plots were created based on Cox model analysis.

Results: After screening 550 studies, a total of 3 studies were included, which compared the safety and effectiveness of TAS-102 with or without bevacizumab. Analysis based on Cox regression showed that the combined treatment group had advantages in 6-month (OR= 2.93, 95% CI: 1.72 to 5.00, P<0.0001), 12-month(OR= 2.18, 95% CI: 1.24 to 3.81, P=0.006), and 18-month (OR=3.08, 95% CI: 1.34 to 7.12, P=0.008) OS. The combined treatment group demonstrated superiority in 6-month PFS rates (OR= 2.50, 95% CI: 1.18 to 5.31, P=0.02). The incidence of thrombocytopenia in the dual-drug treatment group was higher (OR= 1.96, 95% CI: 1.14 to 3.36 P=0.01). The proportion of serious adverse events were similar in tow groups (OR= 1.01, 95% CI: 0.76 to 1.34 P=0.93).

Conclusion: Bevacizumab combined with TAS-102 could improve the prognosis of patients with mCRC who have failed standard treatment. In terms of side effects, the addition of bevacizumab did not increase serious adverse reactions, but the occurrence of thrombocytopenia was worth noting.

Keywords: TAS-102; bevacizumab; colorectal cancer; meta-analysis 3; survival.

Figure 1

Flow graph of selection of included studies.

Figure 2

Forest plot of the meta-analysis comparing TAS-102 plus bevacizumab and TAS-102 in mCRC patients in terms of survival outcomes based on the Cox hazard model. (A) Overall survival. (B) Progress free survival. Horizontal lines represent 95% confidence intervals (CIs). df, degrees of freedom.

Figure 3

Forest plot of pooled relative risk for overall survival from included studies. (A) 6-month overall survival. (B) 12-month overall survival. (C) 18-month overall survival. Horizontal lines represent 95% confidence intervals (CIs). M-H, Mantel-Haenszel; df, degrees of freedom; OS, overall survival.

Figure 4

Forest plot of pooled relative risk for progress free survival from included studies. (A) 3-month progress free survival. (B) 6-month progress free survival. Horizontal lines represent 95% confidence intervals (CIs). M-H, Mantel-Haenszel; df, degrees of freedom; DFS, disease-free survival.

Figure 5

Forest plot of pooled relative risk for disease control rates from included studies. Horizontal lines represent 95% confidence intervals (CIs). M-H, Mantel-Haenszel; df, degrees of freedom; DCR, disease control rate.

Figure 6

Pooled analysis for adverse effects. (A) The incidence of sever AEs (grade≥ 3), (B–H) represent the different side effects. Horizontal lines represent 95% confidence intervals (CIs). M-H, Mantel-Haenszel; df, degrees of freedom; AE, adverse effect.