Efficacy and safety of fruquintinib in refractory metastatic colorectal cancer: a systematic review and meta-analysis.
Abstract
Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality, emphasizing the need for effective later-line therapies. Fruquintinib, a selective vascular endothelial growth factor receptor (VEGFR)1-3 inhibitor, has emerged as a promising option for refractory mCRC. This systematic review and meta-analysis evaluates its efficacy and safety, both as monotherapy and in combination with programmed death-1 (PD-1) inhibitors.
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across PubMed, Embase, Online Vendor of International Databases (OVID), Cochrane Library, and ClinicalTrials.gov (2010-2025). Included studies were randomized controlled trials (RCTs) or real-world data on fruquintinib in mCRC after at least two prior therapies. Real-world evidence was included to complement RCT findings, as it captures broader populations, treatment patterns, and outcomes not fully reflected in controlled trial settings. Primary outcomes were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Pooled hazard ratios (HRs) and event rates were calculated using a random-effects model.
Fifteen studies were included; 12 qualified for meta-analysis (n=3,703). Fruquintinib improved PFS [HR =0.30; 95% confidence interval (CI): 0.26-0.35] and OS (HR =0.66; 95% CI: 0.57-0.76) <i>vs</i>. placebo. ORR was 4.9% (95% CI: 3.2-6.6%); DCR was 62.2% (95% CI: 57.1-67.3%). Combination therapy with PD-1 inhibitors was associated with a modestly higher ORR in observational data; however, this finding requires confirmation in randomized studies (7.8% <i>vs</i>. 4.0%, P=0.04). In cross-study comparisons, monotherapy appeared to yield numerically longer PFS, although this was not based on head-to-head trials. AEs occurred in 86.7%, with grade ≥3 in 30.9%, most often hypertension (8.1%) and hand-foot skin reaction (5.8%). High heterogeneity was observed for several outcomes including AEs and DCR.
Fruquintinib significantly improves PFS and disease control in refractory mCRC with manageable toxicity. Limitations include heterogeneity across studies, with most conducted in predominantly Chinese cohorts. Further studies should explore optimal combination strategies and biomarker-based selection.
EDRN PI Authors
Medline Author List
- Bellamkonda A
- Cheloff A
- Giri S
- Ingawale S
- Kuppili S
- Lella VV
- Nimmagadda R
- Oberstein P
- Shaukat A
- Suvvari TK
- Udaikumar J