Real-world efficacy and safety of fruquintinib plus PD-1 inhibitors with or without radiotherapy in refractory metastatic colorectal cancer: a single-center retrospective cohort study.

BACKGROUND: Patients with microsatellite-stable (MSS) refractory metastatic colorectal cancer (mCRC) derive little benefit from immune checkpoint inhibitors. Whether fruquintinib and localized radiotherapy improve outcomes when combined with programmed death-1 (PD-1) inhibitors remains uncertain in routine practice.This study aimed to evaluate and compare the real-world efficacy and safety of fruquintinib monotherapy (FM), fruquintinib plus a PD-1 inhibitor (FP), and the trimodal combination of fruquintinib, a PD-1 inhibitor, and concurrent radiotherapy (FPR) in refractory mCRC.

METHODS: This single-center retrospective cohort study included 145 heavily pretreated patients with mCRC who had progressed after at least two systemic treatment lines. Propensity score matching (PSM) was used to address baseline imbalances among the three groups. Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) every two to three treatment cycles according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

RESULTS: Among the pre-matched cohort (n=145), baseline characteristics were significantly imbalanced across groups regarding brain, lymph node, and bone metastases. After 1:1:1 PSM (n=16 per group), all baseline characteristics achieved statistical balance (P>0.05). Post-PSM analysis demonstrated that both the FP (median PFS: 5.0 months; P=0.04) and FPR groups (median PFS: 7.2 months; P=0.002) significantly prolonged PFS compared with the FM group (median PFS: 3.5 months). The FPR cohort achieved a numerically highest disease control rate (87.5% vs. 62.5% for FM/FP; P=0.20). Multivariable Cox regression confirmed combination therapy as an independent predictor of favorable PFS (P=0.004). Median OS did not differ significantly among the matched arms (P=0.62). Grade 3-4 toxicities were infrequent and comparable across all groups (P>0.05).

CONCLUSIONS: Fruquintinib combined with a PD-1 inhibitor, with or without concurrent radiotherapy, was associated with significantly longer PFS than fruquintinib alone in refractory mCRC, while maintaining a manageable safety profile. These findings provide preliminary real-world support for fruquintinib-based combination strategies, but prospective validation is required.