Efficacy, safety, and predictors of fruquintinib plus anti-programmed death receptor-1 (PD-1) antibody in refractory microsatellite stable metastatic colorectal cancer in a real-world setting: a retrospective cohort study.

Background: Patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) have few alternatives for salvage therapy and a large unmet clinical need. Preclinical studies demonstrate that fruquintinib combined with anti-programmed death protein 1 (PD-1) has a synergistic anti-tumor effect. But a few phase 2 clinical studies show inconsistent efficacy of this combination therapy in CRC. The aim of this study was to investigate the efficacy, safety, and predictors of fruquintinib plus PD-1 antibodies in refractory MSS metastatic CRC (mCRC) in a real-world setting. Methods: We performed a retrospective single-center analysis to assess the outcomes of patients with MSS mCRC who were treated with fruquintinib plus anti-PD-1 antibodies subsequent to the failure of standard therapies at the Hunan Cancer Hospital. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were reviewed and evaluated. The primary endpoint was OS. The impact on OS and PFS was examined using the Cox regression model. Results: Between 1 January 2019 and 30 June 2022, we enrolled 70 eligible patients. The median follow-up was 17.2 months (range, 5.3-32.9 months). The median OS (mOS) and median PFS (mPFS) were 19.48 and 5.5 months respectively. The ORR was 11.43% and the DCR was 84.29%. Multivariate Cox regression analysis reveals liver metastasis (LM) without local treatment was a risk factor for OS [hazard ratio (HR) =5.31, P=0.0184], whereas that with local treatment (HR =2.19, P=0.263) was not. The most common adverse events were hand-foot syndrome (37.14%), hypertension (34.29%), mucositis oral (32.86%). No serious adverse effects or adverse effect-related deaths were reported. There were no instances of severe adverse effects or deaths related to adverse effects reported. Conclusions: Our study indicates that the combination of fruquintinib and anti-PD-1 antibodies can improve the OS and PFS with a tolerable toxicity profile for Chinese patients with refractory MSS mCRC. LM without local therapy is a negative prognostic factor for OS, but those with local treatment can significantly prolong survival. We require additional well-structured, prospective, and extensive studies to confirm and validate these findings.