Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis

Background: BRAF inhibitor and dual BRAF/MEK inhibitors have been approved for the treatment of BRAF-mutated melanoma. Cutaneous squamous cell carcinoma (cuSCC) is an adverse event associated with these drugs. The contribution of BRAF inhibitor and dual BRAF/MEK inhibitors to cuSCC are still unknown. We performed this meta-analysis to determine the overall incidence and relative risk of cuSCC in cancer patients treated with these drugs. Results: A total of 7,442 patients from 24 primary studies were included. The incidences of all-grade and high-grade cuSCC in cancer patients treated with BRAF inhibitor were 12.5% (95% CI: 10.8-14.6%) and 11.6% (95% CI: 9.8-13.8%), and dual BRAF/MEK inhibitors were 3.0% (95% CI: 2.0-4.5%) and 2.8% (95% CI: 1.9-4.0%), respectively. On subgroup analysis and meta-regression, the incidence of cuSCC did not vary with tumor type, study design and specific drug used. The use of single agent BRAF inhibitor significantly increased the risk of developing cuSCC comparing with dual BRAF/MEK inhibitors for all-grade (RR 4.72, 95% CI: 2.42-9.20) and high-grade (RR 4.92, 95% CI: 2.64-9.16) in cancer patients. Materials and Methods: The databases of PubMed, Embase and abstracts published in ASCO proceedings were searched for relevant studies from January 2000 to June 2017. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. Conclusions: BRAF inhibitor significantly increases the risk of developing cuSCC compared with dual BRAF/MEK inhibitors in cancer patients. Clinicians should be aware of the risks of cuSCC with the administration of these drugs in cancer patients.