LBI-HTA - Publications - Search - Dabrafenib (Tafinlar®) in previously untreated subjects with BRAF mutation-positive advanced (stage III) or metastatic (stage IV) melanoma

Semlitsch, T. and Zengerer, A. and Jeitler, K. (2013): Dabrafenib (Tafinlar®) in previously untreated subjects with BRAF mutation-positive advanced (stage III) or metastatic (stage IV) melanoma. DSD: Horizon Scanning in Oncology 42.

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Abstract

Mutations of the BRAF gene are present in about 50% of all melanomas and 80-90% of these BRAF-positive melanomas show a V600E mutation. In Austria, about 9% of all patients diagnosed with melanoma have already disseminated tumors or died from melanoma. Considering this and the proportion of BRAF mutations in melanoma, the number of patients with BRAF-positive metastatic melanoma each year may be assumed to be about 65 in Austria.

Dabrafenib, a selective ATP-competitive rapidly accelerated fibrosarcoma kinase inhibitor, inhibits all types of BRAF protein kinase. In May 2013 dabrafenib was approved by the FDA for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E mutation, and in August 2013 by the EMA for the treatment of adult patients with unresectable or metastatic melanoma with all types of BRAF V600 mutations.

To date, interim results of one phase III trial and results of two phase II trials have been published. In the multicentre, open-label, randomised controlled phase III trial (BREAK-3), dabrafenib is investigated in comparison to standard chemotherapy with dacarbazine (DTIC) in 250 patients with BRAF-mutant advanced or metastatic melanoma. After a median follow-up of 10 months a significantly increased progression-free survival (PFS) of about 4 months and a significantly higher objective response rate (ORR) in favour of the dabrafenib group has been reported (59% vs. 24%). The analysis of overall survival (OS) after 15 months of follow-up showed no difference between the study groups, but data were still premature. About 10% of the patients with dabrafenib developed squamous cell carcinoma of the skin while no such adverse event occurred in the DTIC group. For the patients’ quality of life no meaningful data were available.

In summary, these results indicate higher response rates and a longer progression-free survival with dabrafenib compared to standard chemotherapy, but there is a rather high toxicity and a rapid development of secondary cutaneous squamous cancer. Furthermore, meaningful data on the patients’ quality of life are missing and the actual costs for the treatment of melanoma patients with dabrafenib are yet unknown for Austria.

Item Type:DSD: Horizon Scanning in Oncology
Keywords:Melanoma, BRAF, V600, skin cancer, Dabrafenib, Tafinlar®
Subjects:WB Practice of medicine > WB 300-962 Therapeutics
QZ Pathology > QZ 200-380 Neoplasms.Cysts
WR Dermatology
QV Pharmacology, toxicology, pharmacy > QV 60-370 Pharmacology
Language:English
Series Name:DSD: Horizon Scanning in Oncology 42
Deposited on:08 Nov 2013 17:02
Last Modified:08 Nov 2013 17:09

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