Efficacy, safety and predictors of combined fruquintinib with programmed death-1 inhibitors for advanced microsatellite-stable colorectal cancer: A retrospective study

BACKGROUND: Research findings have revealed that combining anti-angiogenesis inhibitors with programmed death-1(PD-1) inhibitors can reverse the immunosuppressive tumor microenvironment and enhance the antitumor immune response. To explore the therapeutic options for breaking immune tolerance in microsatellite stability (MSS) or mismatch repair-proficiency (pMMR) advanced colorectal cancer (CRC), we assessed the efficacy, safety and predictors of the fruquintinib and PD-1 inhibitors combination in patients with MSS/pMMR advanced CRC in a real-world environment. METHODS: We conducted a single-center retrospective study by collecting relevant data on patients with MSS/pMMR advanced CRC who received fruquintinib coupled with PD-1 inhibitors in the First Affiliated Hospital of Zhengzhou University between August 2019 and November 2021, focusing on progression-free survival. RESULTS: We enrolled 110 eligible patients in this study between August 2019 and November 2021. At the deadline (January 20, 2022), 13 patients had objective responses. The objective response rate was 11.8% (13/110, 95% confidence interval [CI]: 6.4-18.2), the disease control rate was 70.0% (82/110, 95% CI: 60.9-78.2), and the progression-free survival was 5.4 months (95% CI: 4.0-6.8). Liver metastases (hazard ratio [HR]: 0.594, 95% CI: 0.363-0.973, P<0.05), alkaline phosphatase elevation (ALP>160U/L) (HR: 0.478, 95%CI: 0.241-0.948, P<0.05), fibrinogen elevation (FIB>4g/L) (HR: 0.517, 95% CI: 0.313-0.855, P<0.05), and an increase in the ALP level from the baseline after treatment (HR: 1.673, 95% CI: 1.040-2.690, P<0.05) were negative predictors of the progression-free survival. A total of 101 of 110 patients experienced treatment-related adverse events, including 14 who experienced grade 3 or above treatment-related adverse events, and no treatment-related deaths occurred. Hypertension was the most frequently encountered grade 3 treatment-related adverse event. CONCLUSION: Fruquintinib combined with PD-1 inhibitors has antitumor activity and manageable safety in treating patients with MSS/pMMR advanced CRC. Liver metastases, ALP level and FIB level might be a prediction of the patient response to this therapy.