Treatment outcomes of fruquintinib combined with PD-1 inhibitors in advanced colorectal cancer: a reconstructed patient-level meta-analysis of retrospective real-world studies.

Fruquintinib is an established treatment option for patients with advanced colorectal cancer (CRC) who have progressed after standard therapies, including oxaliplatin- and irinotecan-based chemotherapy. Although this population generally shows limited sensitivity to anti-PD-1/PD-L1 immunotherapy, the combination of fruquintinib and PD-1 inhibitors has been widely used in clinical practice. In this reconstructed patient-level meta-analysis, we aimed to characterize survival outcomes reported in retrospective real-world studies evaluating fruquintinib combined with PD-1 inhibitors. Public databases, including PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), were systematically searched on January 26, 2026.

Patient-level survival data were reconstructed from published Kaplan-Meier curves using the "IPDfromKM" package in R. The "survival" package was used to analyze reconstructed overall survival (OS) and progression-free survival (PFS). The "meta" package was used to pool objective response rate (ORR) and disease control rate (DCR). A total of 10 retrospective studies involving 609 patients were included, all conducted in China.

The reported median OS ranged from 14.9 to 19.5 months, and the pooled median OS was 15.7 months. The reported median PFS ranged from 3.8 to 7.0 months, and the pooled median PFS was 5.5 months. The pooled ORR was 12% (95% CI, 7-18), and the pooled DCR was 74% (95% CI, 68-81). No significant publication bias was detected in the analyses of response rates.

This reconstructed patient-level meta-analysis provides a descriptive summary of reported outcomes associated with fruquintinib combined with PD-1 inhibitors in patients with advanced CRC across retrospective real-world studies.

However, safety outcomes were not systematically reported and therefore could not be comprehensively evaluated. Given the absence of a comparator group, the current evidence does not allow assessment of whether the addition of PD-1 inhibitors improves outcomes compared with fruquintinib monotherapy. Prospective randomized controlled trials are warranted to further characterize the clinical outcomes and safety profile of this treatment strategy.