Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib Academic Article uri icon

abstract

  • PURPOSE:To report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma. METHODS:BRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS. RESULTS:For BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response. CONCLUSION:Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive.

authors

  • Long, GV
  • Weber, JS
  • Infante, JR
  • Kim, KB
  • Daud, A
  • Gonzalez, R
  • Sosman, JA
  • Hamid, O
  • Schuchter, L
  • Cebon, J
  • Kefford, RF
  • Lawrence, D
  • Kudchadkar, R
  • Burris, HA
  • Falchook, GS
  • Algazi, A
  • Lewis, K
  • Puzanov, I
  • Ibrahim, N
  • Sun, P
  • Cunningham, E
  • Kline, AS
  • Del Buono, H
  • McDowell, DO
  • Patel, K
  • Flaherty, KT

publication date

  • 2016