Russo Irene, Zorzetto Ludovica, Frigo Anna Chiara, Chiarion Sileni Vanna, Alaibac Mauro
Unit of Dermatology, University of Padua, Via Gallucci 4, 35128 Padova, Italy.
Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences University of Padua Via Loredan, 18, 35131 Padova, Italy.
Eur J Dermatol. 2017 Oct 1;27(5):482-486. doi: 10.1684/ejd.2017.3069.
Patients with advanced melanoma have a poor prognosis. Since the discovery of BRAF mutations in cutaneous melanoma, new pharmacological agents have been developed to inhibit this target. Although the survival of patients with advanced melanoma has improved with BRAF inhibitors, the emergence of drug resistance and the high incidence of cutaneous side effects represent important limitations. The aim of our study was to compare the incidence of cutaneous side effects between BRAF inhibitor monotherapy and BRAF and MEK inhibitor combination therapy in our cohort of patients. This study was a longitudinal prospective observational study. The study population comprised 83 patients with advanced cutaneous melanoma presenting with BRAF V600 mutation. The inclusion criteria included: age above 18 years, metastatic cutaneous melanoma or melanoma with high risk of metastasis, the presence of BRAF V600 mutation, and treatment with BRAF inhibitors or a combination of BRAF and MEK inhibitors. The majority of patients developed skin toxicity during treatment. The most common cutaneous side effects were localized hyperkeratosis and verrucous keratosis. Other cutaneous side effects observed were photosensitivity, squamous cell carcinoma, and keratoacanthoma. Our results indicate that cutaneous side effects are generally observed during BRAF inhibitor monotherapy and are significantly different from those observed in patients treated with combination therapy.
晚期黑色素瘤患者预后较差。自皮肤黑色素瘤中发现BRAF突变以来，已开发出新的药物制剂来抑制该靶点。尽管BRAF抑制剂改善了晚期黑色素瘤患者的生存率，但耐药性的出现和皮肤副作用的高发生率仍是重要的局限性。我们研究的目的是比较在我们的患者队列中，BRAF抑制剂单药治疗与BRAF和MEK抑制剂联合治疗之间皮肤副作用的发生率。本研究是一项纵向前瞻性观察研究。研究人群包括83例存在BRAF V600突变的晚期皮肤黑色素瘤患者。纳入标准包括：年龄18岁以上、转移性皮肤黑色素瘤或有高转移风险的黑色素瘤、存在BRAF V600突变，以及接受BRAF抑制剂或BRAF与MEK抑制剂联合治疗。大多数患者在治疗期间出现皮肤毒性。最常见的皮肤副作用是局限性角化过度和疣状角化病。观察到的其他皮肤副作用有光敏性、鳞状细胞癌和角化棘皮瘤。我们的结果表明，BRAF抑制剂单药治疗期间通常会观察到皮肤副作用，且与联合治疗患者中观察到的副作用有显著差异。
