Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Background Vemurafenib has been linked to dermatological adverse events in patients with melanoma, including an increased risk of rash, cutaneous squamous cell carcinoma, photosensitivity reaction and keratoacanthoma. However, there has been no systematic attempt to assess the dermatological toxicity data of vemurafenib associated with melanoma treatment. Aim To evaluate the point prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma. Methods Searches were conducted of the electronic databases PubMed and EMBASE and of conference abstracts published by the American Society of Clinical Oncology. Eligible studies included prospective clinical trials and expanded-access programmes (i.e. outside a clinical trial) of patients with melanoma assigned to vemurafenib treatment. Outcomes included prevalence of dermatological toxicities treated with vemurafenib. Statistical analyses were performed using the R2.8.1 meta package. Results In total, 11 studies comprising 4197 patients were included in the meta-analysis. For patients assigned to vemurafenib, the overall prevalence of all-grade cutaneous squamous cell carcinoma (cSCC) was 18.00% (95% CI 12.00-26.00%), rash 45.00% (95% CI 34.00-57.00%), photosensitivity reaction (PR) 30.00% (95% CI 23.00-38.00%), keratoacanthoma (KA) 10.00% (95% CI 6.00-15.00%) and hand-foot skin reaction (HFSR) 9.00% (95% CI 4.00-20.00%), while the prevalence of high-grade events was: cSCC 16.00% (95% CI 11.00-23.00%), rash 12.00% (95% CI 3.00-38.00%), PR 4% (95% CI 2.00-8.00%) and KA 6.00% (95% CI 5.00-7.00%). Conclusion The most frequent dermatological toxicities associated with vemurafenib treatment in patients with melanoma were cSCC, rash, PR and KA. These data may be useful for estimation of the efficacy and safety of the drug during clinical treatment and for reducing the prevalence of adverse reactions to vemurafenib treatment in patients with melanoma.