PMID- 27246822
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20220310
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 11
IP  - 3
DP  - 2016 Jun
TI  - Dabrafenib plus Trametinib: a Review in Advanced Melanoma with a BRAF (V600) 
      Mutation.
PG  - 417-28
LID - 10.1007/s11523-016-0443-8 [doi]
AB  - The BRAF inhibitor dabrafenib (Tafinlar((R))) and the MEK inhibitor trametinib 
      (Mekinist((R))) are indicated, as monotherapy or in combination with each other, 
      for the treatment of patients with unresectable or metastatic melanoma with a 
      BRAF (V600) mutation. This article reviews the therapeutic efficacy and 
      tolerability of combination treatment with dabrafenib and trametinib in this 
      indication and summarizes relevant pharmacological data. Dabrafenib plus 
      trametinib significantly prolonged progression-free survival (PFS) and overall 
      survival (OS), improved objective response rates (ORRs) and preserved 
      health-related quality of life (HR-QOL) to a greater extent than dabrafenib (in 
      the double-blind COMBI-d study) and vemurafenib (in the open-label COMBI-v study) 
      in two large, randomized, phase III studies in treatment-naive patients with 
      unresectable or metastatic melanoma with BRAF (V600E/K) mutation. Limited 
      treatment benefit with the combination was also seen in patients who had 
      progressed on prior BRAF inhibitor therapy, as indicated by ORRs of </= 15 % and 
      stable disease in </= 50 % of patients in small phase I and II studies. Combination 
      therapy did not increase overall toxicity relative to dabrafenib or vemurafenib 
      monotherapy, with most adverse events (AEs) mild or moderate in severity and 
      generally manageable. Fewer skin-related AEs (e.g. cutaneous malignancies, 
      hyperkeratinosis and hand-foot syndrome) were reported with combination therapy 
      than with dabrafenib or vemurafenib, probably because of reduced paradoxical 
      activation of the MAPK pathway. Thus, dabrafenib plus trametinib provides an 
      important treatment option for patients with BRAF (V600) mutation-positive 
      unresectable or metastatic melanoma.
FAU - Dhillon, Sohita
AU  - Dhillon S
AD  - Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand. 
      demail@springer.com.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Oximes)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidinones)
RN  - 33E86K87QN (trametinib)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - QGP4HA4G1B (dabrafenib)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Humans
MH  - Imidazoles/administration & dosage/pharmacology/*therapeutic use
MH  - Melanoma/*drug therapy/pathology
MH  - Mutation
MH  - Oximes/administration & dosage/pharmacology/*therapeutic use
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Pyridones/administration & dosage/pharmacology/*therapeutic use
MH  - Pyrimidinones/administration & dosage/pharmacology/*therapeutic use
EDAT- 2016/06/02 06:00
MHDA- 2017/10/31 06:00
CRDT- 2016/06/02 06:00
PHST- 2016/06/02 06:00 [entrez]
PHST- 2016/06/02 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
AID - 10.1007/s11523-016-0443-8 [pii]
AID - 10.1007/s11523-016-0443-8 [doi]
PST - ppublish
SO  - Target Oncol. 2016 Jun;11(3):417-28. doi: 10.1007/s11523-016-0443-8.