Abstract: Objective To evaluate the efficacy and safety of fruquintinib alone or in combination with immune checkpoint inhibitor (ICI) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC)in third⁃line or above treatment. Methods Patients with pMMR/MSS type mCRC admitted to the Department of Oncology, Renmin Hospital of Wuhan University, from January 2020 to April 2024 were selected as the research objects. The prognoses, efficacies and safeties of fruquintinib alone and in combination with ICI were compared in the unadjusted model and the propensity score matching. Results A total of 104 patients were included in the analysis, 33 in the fruquintinib group and 71 in the fruquintinib combined with ICI group. Compared to the fruquintinib group, the median progression⁃free survival was longer in the fruquintinib combined ICI group (3.0 months vs 4.5 months; HR=0.55, 95%CI: 0.33-0.89）. However, there were no significant differences in the median overall survival (10.1 months vs 13.1 months）, the objective response rate (9.1% vs 11.3%) and the disease control rate (51.5% vs  66.2%)between the two groups (all P>0.05）. Similar results were obtained in the analysis of the propensity score matching. The adverse events of grade 3 or above in both groups mainly included hand⁃foot⁃skin reaction, thrombocytopenia and leukopenia. The incidence of grade 3 or above adverse events was 30. 3% in the fruquintinib group and 36.6% in the fruquintinib combined with ICI group (P=0.529）. Conclusions Compared with fruquintinib, fruquintinib combined with ICI provides benefits in the progression⁃free survival for pMMR/MSS type mCRC patients in third⁃line or above treatment with controllable safety, which is worthy of further study.

Key words: Metastatic colorectal cancer, Microsatellite stable, Fruquintinib, Immune checkpoint inhibitor, Later?line treatment