Long-Term Outcomes in Patients With BRAF V600–Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib Academic Article uri icon

abstract

  • Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

authors

  • Long, Georgina V
  • Eroglu, Zeynep
  • Infante, Jeffrey
  • Patel, Sapna
  • Daud, Adil
  • Johnson, Douglas B
  • Gonzalez, Rene
  • Kefford, Richard
  • Hamid, Omid
  • Schuchter, Lynn
  • Cebon, Jonathan
  • Sharfman, William
  • McWilliams, Robert
  • Sznol, Mario
  • Redhu, Suman
  • Gasal, Eduard
  • Mookerjee, Bijoyesh
  • Weber, Jeffrey
  • Flaherty, Keith T

publication date

  • 2018