Vascular endothelial growth factor receptor (VEGFR) -tyrosine kinase inhibitors combined with programmed death receptor-1 (PD-1) inhibitors as third- or later-line treatment in patients with microsatellite-stable (MSS) metastatic colorectal cancer (m

68 Background: Microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to programmed death receptor-1 (PD-1) inhibitors. Recent studies suggest that combining vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs) with PD-1 inhibitors may enhance the anti-cancer activity for mCRC patients. Multiple antiangiogenic drugs have been approved by the FDA and NMPA for the treatment of later-line mCRC. Nevertheless, the effects of various anti-angiogenic drugs when used in combination with immunotherapy for mCRC treatment is not yet fully established. Methods: We conducted a non-interventional, retrospective study. Data were compiled from patients with mCRC at Shandong Cancer Hospital. Eligible patients must have received a combination of anti-angiogenic drugs and PD-1 inhibitors following at least two lines of standard treatment. The treatment period spanned from August 2019 to April 2024. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Results: At the cut-off date (April 29th, 2024), 79 eligible patients were available for analysis. Of these, 49 patients received fruquintinib in combination with PD-1 inhibitors (F group), 30 patients received investigator-selected other anti-angiogenic agents in combination with PD-1 inhibitors (NF group). The baseline characteristics of the two groups were well balanced. The median overall survival (OS) was significantly longer in the F group compared to the NF group (hazard ratio [HR]: 0.36, 95% CI 0.14-0.96, P=0.042). The median OS was not reached (95% CI 21.1-NA) in the F group, whereas it was 19.1 months (95% CI 12.6-NA) in the NF group. Subgroup analyses of OS were generally consistent with benefit in the whole population across nearly all subgroups. In contrast to NF group, individuals in F group demonstrated a significant enhancement in overall survival (OS) when patients had received prior bevacizumab (HR: 0.26, 95% CI 0.07-0.75, P=0.015), had no prior treatment with cetuximab (HR: 0.23, 95% CI 0.26-0.97, P=0.045), or had experienced surgical resection at baseline (HR: 0.34, 95% CI 0.12-0.95, P=0.041). The median PFS between two groups showed no statistically significant difference (HR: 0.65, 95% CI 0.38-1.13, P=0.127), F group 6.1 months (95% CI 4.6-10.3) versus NF group 4.4 months (95% CI, 3.0-7.5). Conclusions: Fruquintinib demonstrated improved OS over other anti-angiogenic agents when combined with immunotherapy for third or later-line MSS mCRC treatment.