Toxicities of Fruquintinib in Gastrointestinal Malignancies: A Systematic Review and Meta-Analysis
In brief
Fruquintinib raises severe hypertension risk ninefold and skin toxicity 26-fold
In four randomized trials of 1,872 patients with gastrointestinal cancers, fruquintinib increased grade at least 3 hypertension about nine times and grade at least 3 hand-foot skin reaction about 26 times compared with control therapy. It also modestly doubled any-grade proteinuria, while serious bleeding and clotting events were rare and uncertain. Clinicians should monitor blood pressure, skin, and urine early when starting this drug.
- Journal
- Oncology research (Q1)
- Published
- 14 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Daniel Thomas Jones, Tajveer Sangha, Arman Manjikian, Micheal Ghobrial, Qasim Shawesh, Emaan Tiwana, et al.
- PMID
- 42769859
- DOI
- 10.32604/or.2026.078524
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 27 September 2026): Systematic review of fruquintinib toxicities in gastrointestinal cancers
Abstract
Backgrounds: Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR)-1/2/3 inhibitor approved for previously treated metastatic colorectal cancer. As its use expands across gastrointestinal (GI) malignancies and combination regimens, randomized evidence is needed to define the toxicity profile most relevant to clinical monitoring, particularly hypertension, dermatologic toxicity, renal toxicity, bleeding, and thrombotic events. The objective of this study was to synthesize randomized controlled trial evidence to quantify the incidence and relative risk of key toxicities associated with fruquintinib in gastrointestinal malignancies. Methods: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception through 1 January 2026 for phase II-III randomized controlled trials of fruquintinib in GI cancers reporting hypertension, proteinuria, hemorrhage, venous thromboembolism (VTE), and hand-foot skin reaction or palmar-plantar erythrodysesthesia (HFSR/PPE). Trial-reported CTCAE adverse events were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using Mantel-Haenszel random-effects models. Exploratory subgroup analyses were performed in metastatic colorectal cancer (mCRC). Results: Four randomized trials (n = 1872) were included. Fruquintinib significantly increased grade ≥3 hypertension (RR 9.01, 95% CI 4.67-17.40) and grade ≥3 HFSR/PPE (RR 26.00, 95% CI 6.42-105.29). Any-grade proteinuria was also increased (RR 1.89, 95% CI 1.30-2.74). Grade ≥3 hemorrhage occurred at low absolute rates and was numerically higher with fruquintinib, but the pooled estimate did not reach statistical significance (RR 1.82, 95% CI 0.92-3.61). VTE estimates were imprecise because of sparse events (any-grade VTE: RR 1.23, 95% CI 0.53-2.88; grade ≥3 VTE: RR 1.96, 95% CI 0.52-7.36). Conclusions: In randomized evidence across GI malignancies, the principal safety signals associated with fruquintinib are grade ≥3 hypertension and grade ≥3 HFSR/PPE, together with increased any-grade proteinuria. Grade ≥3 hemorrhage was uncommon and numerically higher, whereas VTE estimates remained imprecise. These findings support early blood pressure optimization, proactive dermatologic management, routine urinalysis monitoring, and individualized assessment of bleeding and thrombotic risk when initiating therapy.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.