Objective: Dabrafenib, an inhibitor of mutated BRAF, has significant clinical activity in melanoma patients but is linked to a spectrum of cutaneous toxicities. Thus, our meta-analysis was conducted to evaluate the type, incidence and risks of dermatological toxicities from dabrafenib.
Methods: Systematic searches were performed using electronic databases such as Embase and PubMed and conference abstracts published by the American Society of Clinical Oncology. Eligible studies were limited to prospective phase I, II and III clinical trials and expanded-access (ie, outside clinical trials) programmes of melanoma patients receiving dabrafenib monotherapy (150 mg, twice daily) or combination therapy of dabrafenib (150 mg, twice daily) plus trametinib (2 mg, once daily). The outcomes were mainly the incidence rate and risk of all-grade cutaneous toxicities associated with dabrafenib in melanoma patients.
Results: Twenty trials comprising a total of 3359 patients were included in the meta-analysis. The meta-analysis showed that the overall incidence of all-grade rash for melanoma patients assigned dabrafenib was 30.00% (95% CI 0.07 to 0.71), cutaneous squamous-cell carcinoma (cSCC) 16.00% (95% CI 0.11 to 0.24), alopecia 21% (95% CI 0.11 to 0.37), keratoacanthoma (KA) 20.00% (95% CI 0.12 to 0.31), hyperkeratosis (HK) 14.00% (95% CI 0.09 to 0.22) and pruritus 8.00% (95% CI 0.05 to 0.12). All-grade rash occurred in 19.00% (95% CI 0.15 to 0.25), cSCC in 10.00% (95% CI 0.04 to 0.22), alopecia in 6.00% (95% CI 0.03 to 0.12), KA in 6.00% (95% CI 0.04 to 0.09) and pruritus in 2/1265 patients assigned dabrafenib plus trametinib. The summary risk ratio (RR) showed that the combination of dabrafenib with trametinib versus dabrafenib was associated with a significantly increased risk of all-grade rash (RR 1.35, 95% CI 1.01 to 1.80) and a decreased risk of cSCC (RR 0.40, 95% CI 0.18 to 0.89), alopecia (RR 0.19, 95% CI 0.12 to 0.30) and HK (RR 0.25, 95% CI 0.10 to 0.62).
Conclusion: In summary, the most frequent cutaneous adverse reactions from dabrafenib were rash, cSCC, alopecia, KA, HK and pruritus. There was a significantly decreased risk of cSCC, alopecia and HK with the combination of dabrafenib with trametinib versus dabrafenib alone. Clinicians should be aware of these risks and perform regular clinical monitoring.
Keywords: adverse effects; cancer pain; drug administration (others); risk management; side effects of drugs.
© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.