Journal: British journal of pharmacology
This systematic review and meta-analysis evaluated whether hand–foot skin reaction (HFSR) during treatment with VEGFR tyrosine kinase inhibitors (VEGFR-TKIs) correlates with survival outcomes in solid tumors.
Design and methods
- Data sources: MEDLINE, Embase, and Cochrane Central through June 29, 2025.
- Included studies: 32 observational cohorts, totaling 6543 patients on VEGFR-TKIs, of whom 2671 developed HFSR.
- Outcomes: Overall survival (OS) and progression-free survival (PFS).
- Analysis: Random-effects meta-analysis of hazard ratios (HRs), with subgroup analyses by tumor type and specific VEGFR-TKI.
Key findings
- Across all included cancers: Development of HFSR was associated with significantly better outcomes:
- OS: HR 0.54 (95% CI 0.49–0.60).
- PFS: HR 0.59 (95% CI 0.53–0.65).
- Tumor-specific subgroups: Patients with hepatocellular carcinoma, colorectal cancer, and non-small cell lung cancer who developed HFSR had significantly improved OS and PFS compared with those without HFSR.
- Drug-specific subgroups: HFSR predicted better OS and PFS in patients treated with sorafenib, regorafenib, fruquintinib, anlotinib, and cabozantinib.
Clinical implications
- Prognostic role: VEGFR-TKI–induced HFSR appears to function as a positive on-treatment prognostic/surrogate marker for survival rather than just a toxicity signal.
- Management approach: Rather than prompting automatic dose discontinuation, HFSR should trigger early recognition and proactive supportive care (topical measures, dose modification as needed) to preserve both treatment efficacy and quality of life.