Fruquintinib plus sintilimab in previously bevacizumab-treated, pMMR/MSS refractory metastatic colorectal cancer: a phase 2 clinical trial.

BACKGROUND: This study aimed to investigate the efficacy and safety of fruquintinib plus sintilimab in mismatch repair-proficient (pMMR)/microstatellite stable (MSS) refractory metastatic colorectal cancer (mCRC). METHODS: Patients with pMMR/MSS mCRCs who had failed at least 2 lines of standard therapy were enrolled and treated with fruquintinib plus sintilimab in this single arm, phase II clinical trial. The primary endpoint was the 6 month progression-free survival (PFS) rate. RESULTS: A total of 75 patients were included, all of whom had been previously treated with bevacizumab. The 6 month PFS rate was 33.3%. The median PFS (mPFS) was 4.1 months, the median overall survival (mOS) was 15.3 months, the objective response rate (ORR) was 12.5%, and the disease control rate (DCR) was 76.4%. Treatment-related adverse events (TRAEs) occurred in 94.7%, with 18.7% being grade 3 or 4. There were no treatment-related deaths. Patients had a significantly shorter mPFS compared to those without liver metastasis (3.2 versus 7.6 months, P < 0.001). Incorporating Eastern Cooperative Oncology Group (ECOG) score further improved its predictive value for PFS. Those in the high-albumin group showed significantly longer mOS (25.9 versus 11.0 months, P = 0.024), while the high-neutrophil-to-lymphocyte ratio (NLR) group exhibited a significantly shorter mOS (9.3 versus 19.3 months, P = 0.033). CONCLUSIONS: Fruquintinib plus sintilimab showed promising activity and good tolerability in refractory pMMR/MSS mCRC. Liver metastasis was a negative predictor for efficacy and PFS, especially when combined with the ECOG score. Higher baseline albumin and lower NLR predicted longer OS.