Does capecitabine maintenance therapy versus active monitoring confer a survival benefit after first-line treatment of metastatic colorectal cancer? A meta-analysis of randomized controlled trials

Abstract

Abstract Background The maintenance treatment of metastatic colorectal cancer (mCRC) after first-line treatment is still controversial. Meta analysis was used to analyze whether there was survival benefit after first-line treatment of mCRC from the effectiveness and safety of capecitabine maintenance treatment. Methods In April, 2022, the following biomedical electronic databases were searched: PubMed, EMBASE, Google Scholar and Cochrane Library, including capecitabine maintenance therapy versus active monitoring randomized controlled trials (RCTs) and clinical trials (CT) of mCRC patients after first-line treatment. The primary outcome was progression free survival (PFS) of capecitabine maintenance therapy, and secondary outcomes included overall survival (OS), toxicity, and BRAF and RAS gene mutation status. Extract the hazard ratio (HR) of 95% confidence interval (CI) or HR data that can calculate 95% confidence interval (CI). All data were analyzed by Revman5.4 software. Results Five eligible studies included 1672 patients. Meta analysis showed that capecitabine maintenance therapy had more significant benefits for PFS than active monitoring PFS (HR 0.59; 95%CI: 0.52–0.66; P < 0.00001); In addition, capecitabine maintenance therapy was also beneficial to OS (HR 0.85; 95% CI: 0.76–0.95; p = 0.003). Subgroup analysis showed that BRAF/RAS wild-type patients were more likely to benefit from capecitabine maintenance, based on the significant interaction between BRAF/RAS status (P = 0.002). The most common adverse reaction was hand-foot skin reaction to capecitabine maintenance therapy compared with active monitoring (2.3% vs 0.4%; OR 5.53, 95%CI: 1.42–21.58, I2 = 0%, P = 0.01) was slightly increased. Conclusion This meta-analysis suggests that capecitabine was beneficial in PFS and OS compared with active monitoring. Adverse reactions are common but acceptable. Subgroup analysis showed that the differential effect of capecitabine maintenance treatment was beneficial to BARF/RAS wild-type patients. In specific cases, capecitabine monotherapy maintenance therapy can be considered, such as cumulative toxicity to fluoropyrimidine or patient rejection, especially for BRAF/RAS wild-type patients.