Advances in Treatment for Patients Unresectable or Metastatic BRAF V600 Mutated Melanoma

Melanoma is widely prevalent among western populations and is a relatively rare malignancy in the local Chinese population. In local Chinese patients, clinicians should be wary of suspicious pigmented lesions over the extremities, such as the soles, palms, nail beds, or mucous membrane because up to 60% of cases of melanoma in Chinese people are of acral lentiginous type, compared with only 2% in Caucasians. The pigmented type of basal cell carcinoma is the most common subtype of basal cell carcinoma in Hong Kong. Thus, differential diagnoses of pigmented skin lesions in local Chinese should include pigmented basal cell carcinoma in addition to melanoma. The standard treatment of advanced and metastatic disease is chemotherapy with agents such as dacarbazine, with immunotherapy (e.g. interleukin-2) providing an alternative option. However, both treatment modalities are associated with modest effectiveness in terms of response and survival, and with potentially serious side-effects. A phase III clinical trial in patients with metastatic melanoma showed that treatment with the novel immunotherapy ipilimumab - an intravenous, fully humanised immunoglobulin monoclonal antibody - was associated with a response rate of 10.9% and median overall survival of approximately 10 months; however, there were marked immune side-effects. Recently, advances in the knowledge of cell signalling pathways in melanoma - particularly with regard to the role of the serine/threonine kinase v-raf murine sarcoma viral oncogene homolog B1 (BRAF) - have led to the development of targeted biological agents. Vemurafenib is a potent oral small molecule that inhibits the activated form of the oncogenic BRAF V600E mutant. In a recent phase III clinical trial comparing vemurafenib with dacarbazine, treatment with vemurafenib was associated with improved overall survival (median, 13.6 months vs. 9.7 months with dacarbazine), progression-free survival (median, 5.3 months vs. 1.6 months with dacarbazine), and confirmed objective response rate (57.0% vs. 8.6% with dacarbazine) in patients with advanced melanoma at a median follow-up of 12.5 months. This article provides an overview of the features of melanoma in Chinese patients, and the current treatment options for advanced metastatic melanoma. At the time of crossover in 2012, subjects receiving vemurafenib showed higher objective response rate (57.0% vs. 8.6%), complete remission rate (5.6% vs. 1.2%), and partial response rate (51.3% vs. 7.4%), versus those receiving dacarbazine.