Efficacy and safety of fruquintinib combined with immunotherapy in later‑line treatment of metastatic colorectal cancer

For microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), later-line treatments are limited and survival outcomes are poor. The present retrospective analysis evaluated the efficacy and safety of fruquintinib + immune checkpoint inhibitors (ICIs) in MSS/mismatch repair proficient (pMMR) mCRC, having aimed to identify effective, low-toxicity regimens for personalized treatment. The present retrospective study evaluated patients with MSS/pMMR mCRC who had failed at least two prior lines of treatment (all patients had received standard first- and second-line chemotherapy) and were treated with fruquintinib plus programmed death-1 (PD-1) (PD-1 inhibitor combination group) or programmed death-ligand 1 (PD-L1) (PD-L1 inhibitor combination group) inhibitors at the Jiangsu Cancer Hospital (Nanjing, China). Clinical characteristics were collected, and the efficacy, safety and prognostic factors of fruquintinib plus different ICIs were analyzed. A total of 78 patients (PD-1 inhibitor combination group, n=63; PD-L1 inhibitor combination group, n=15) were included. Clinical characteristics did not differ significantly between the two groups (all P>0.05). The objective response rate (7.9 vs. 20.0%; P=0.363), disease control rate (74.6 vs. 60.0%; P=0.418) and median progression-free survival (PFS; 7.0 vs. 8.3 months; P=0.14) were comparable between the groups. Similarly, no significant difference in PFS was observed between patients treated with fruquintinib plus different PD-1 inhibitors (P=0.37). Multivariate Cox regression analysis identified an Eastern Cooperative Oncology Group performance status of 1 (hazard ratio=0.28; P<0.001) as an independent prognostic factor for PFS. The most common adverse events (AEs) were hypothyroidism (31.7 vs. 26.7%), proteinuria (23.8 vs. 33.3%) and hand-foot syndrome (20.6 vs. 33.3%). No AE-related deaths occurred in either group. The present study showed that fruquintinib plus ICIs could improve PFS in MSS mCRC with manageable toxicity, but there was no survival difference between treatment with the PD-1 and PD-L1 combinations.