Objective  To assess the efficacy and safety of anlotinib for patients with metastatic colorectal cancer (mCRC) who had received at least two lines of standard therapy.

  Methods  The clinical data of 53 patients with refractory colorectal cancer treated with anlotinib at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital from September 2014 to August 2016 were collected and analyzed. The efficacy and safety of anlotinib were observed and evaluated.

  Results  Patients were randomly assigned into anlotinib group and placebo group. The median overall survival (OS) times for the anlotiniband groups and the placebo groups were 8.2 months and 9.3 months, respectively. The median progression-free survival (PFS) measures for the anlotinib groups and the placebo groups were 5.03 months and 1.33 months, respectively (hazard ratio, HR=0.27, 95% confidence interval, 95%CI: 0.13-0.54). The objective response rates (ORR) for the two groups were 2.94% and 0, respectively. The disease control rate (DCR) was better in the anlotinib group than in the placebo group (88.24% vs. 36.84%, P<0.00 1). In the 26 patients with RAS/BRAF wild type, the median PFS significantly improved in the anlotinib group compared with that of the placebo group (5.37 months vs. 1.33 months). The DCR of anlotinib was also higher than that of the placebo (93.33% vs. 36.36%, P=0.003). The most common above grade 3 anlotinib-related adverse events were hypertension (17.65%), diarrhea (8.82%), and hand-foot skin reaction (8.82%).

  Conclusions  Anlotinib is effective as a third- or later-line therapy for mCRC, with significant PFS benefits and increased DCR with acceptable toxicity. Therefore, it maybe an option for treating mCRC. Potential benefits for patients with RAS/BRAF wild-type cancer should be confirmed with further clinical trials.