Effect of BRAF Mutation Status on Efficacy of nab-Paclitaxel versus Dacarbazine in Chemotherapy-Naive Patients with Metastatic Melanoma Treated in a Phase III Trsial

J. -J Grob, E. Hersh, M. Del Vecchio, M. P. Brown, R. Kefford, C. Loquai, A. Testori, C. Robert, M. Li, I Elias, M. F. Renschler, A. Hauschild

Research output: Contribution to journalMeeting abstract

Abstract

Question: About 40–50% of melanomas harbor activating mutations of BRAF V600 which are related to poor prognosis. In a phase III trial in chemotherapy-naive, metastatic melanoma patients, nab-pac- litaxel (nab-P) vs dacarbazine (DTIC) demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), assessed by independent radiological review, and a trend toward prolonged overall survival (OS) at the interim survival analy-
sis. The study also explored the effect of BRAF status on the efficacy parameters.

Methods: Chemotherapy-naive patients with stage IV melanoma (M1c stage 65%;elevated LDH 28%) and ECOG performance status 0–1 were randomized to nab-P 150 mg/m2 on days 1, 8 and 15 of a 28-day cycle (n = 264) or DTIC 000 mg/m2 on day 1 of each 21-day cycle (n = 265), independent of BRAF status. Prespecified sub-group analyses of final PFS and interim OS in subgroups by BRAF status (V600E mutant, wild-type, or unknown) were performed.

Results: BRAF mutational status was known in 67% of the patients (ITT); of these, 37% had a V600E mutation (n = 65 nab-P and n = 67 DTIC) and 63% had wild-type BRAF (n = 116 nab-P and n = 108 DTIC). Patient characteristics were balanced within BRAF subgroups. An advantage in the nab-P arm versus DTIC arm was observed for both PFS and interim OS regardless of BRAF mutation
status. For patients with wild-type, V600E, or unknown BRAF mutation status, PFS was 5.4, 5.3 and 3.7 months, respectively, with nab-P versus 2.5, 3.5 and 2.2 months, respectively, with DTIC. Interim OS was 12.7, 16.9 and 11.1 months with nab-P versus 11.1, 11.2 and 9.9 months with DTIC. Poststudy BRAF inhibitor treat- ment was well balanced.

Conclusion: In this phase III trial, treatment effect was independent of BRAF mutation status, benefiting all patients who received nab-P versus DTIC. Based on these results, nab-P can be considered in the chemotherapy armamentarium for chemotherapy-naive patients with metastatic melanoma regardless of their BRAF mutation status.
Original languageEnglish
Article numberP-102
Pages (from-to)56-56
Number of pages1
JournalJDDG - Journal of the German Society of Dermatology
Volume11
Issue numberSupplement 7
Publication statusPublished - 18 Jul 2013
Externally publishedYes

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