PMID- 28052762
OWN - NLM
STAT- MEDLINE
DCOM- 20171128
LR  - 20220331
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Jan 4
TI  - Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib 
      plus cobimetinib in previously untreated metastatic melanoma patients.
PG  - 3
LID - 10.1186/s13045-016-0369-8 [doi]
LID - 3
AB  - BACKGROUND: Metastatic melanoma is an aggressive form of skin cancer with a high 
      mortality rate and the fastest growing global incidence rate of all malignancies. 
      The introduction of BRAF/MEK inhibitor combinations has yielded significant 
      increases in PFS and OS for melanoma. However, at present, no direct comparisons 
      between different BRAF/MEK combinations have been conducted. In light of this, an 
      indirect treatment comparison was performed between two BRAF/MEK inhibitor 
      combination therapies for metastatic melanoma, dabrafenib plus trametinib and 
      vemurafenib plus cobimetinib, in order to understand the relative efficacy and 
      toxicity profiles of these therapies. METHODS: A systematic literature search 
      identified two randomized trials as suitable for indirect comparison: the coBRIM 
      trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of 
      dabrafenib plus trametinib versus vemurafenib. The comparison followed the method 
      of Bucher et al. and analyzed both efficacy (overall survival [OS], 
      progression-free survival [PFS], and overall response rate [ORR]) and safety 
      outcomes (adverse events [AEs]). RESULTS: The indirect comparison revealed 
      similar efficacy outcomes between both therapies, with no statistically 
      significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% 
      confidence interval [CI] 0.68 - 1.30), PFS (HR 1.05, 95% CI 0.79 - 1.40), or ORR 
      (risk ratio [RR] 0.90, 95% CI 0.74 - 1.10). Dabrafenib plus trametinib differed 
      significantly from vemurafenib plus cobimetinib with regard to the incidence of 
      treatment-related AE (RR 0.92, 95% CI 0.87 - 0.97), any AE grade >/=3 (RR 0.71, 95% 
      CI 0.60 - 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 - 0.99). 
      Several categories of AEs occurred significantly more frequently with vemurafenib 
      plus cobimetinib, while some occurred significantly more frequently with 
      dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred 
      significantly more frequently with vemurafenib plus cobimetinib and no severe AE 
      occurred significantly more frequently with dabrafenib plus trametinib. 
      CONCLUSIONS: This indirect treatment comparison suggested that dabrafenib plus 
      trametinib had comparable efficacy to vemurafenib plus cobimetinib but was 
      associated with reduced adverse events.
FAU - Daud, Adil
AU  - Daud A
AD  - Medicine and Dermatology, University of California, 1600 Divisadero Street Rm A 
      743, San Francisco, CA, 94143, USA. Adil.Daud@ucsf.edu.
FAU - Gill, Japinder
AU  - Gill J
AD  - PAREXEL International, Chandigarh, India.
FAU - Kamra, Sheily
AU  - Kamra S
AD  - PAREXEL International, Chandigarh, India.
FAU - Chen, Lei
AU  - Chen L
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Ahuja, Amit
AU  - Ahuja A
AD  - PAREXEL International, Chandigarh, India.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170104
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Azetidines)
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Oximes)
RN  - 0 (Piperidines)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidinones)
RN  - 0 (Sulfonamides)
RN  - 207SMY3FQT (Vemurafenib)
RN  - 33E86K87QN (trametinib)
RN  - ER29L26N1X (cobimetinib)
RN  - QGP4HA4G1B (dabrafenib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Azetidines/administration & dosage
MH  - Female
MH  - Humans
MH  - Imidazoles/administration & dosage
MH  - Indoles/administration & dosage
MH  - Male
MH  - Melanoma/complications/*drug therapy/mortality/pathology
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Oximes/administration & dosage
MH  - Piperidines/administration & dosage
MH  - Pyridones/administration & dosage
MH  - Pyrimidinones/administration & dosage
MH  - *Randomized Controlled Trials as Topic
MH  - Sulfonamides/administration & dosage
MH  - Treatment Outcome
MH  - Vemurafenib
MH  - Young Adult
PMC - PMC5209913
OTO - NOTNLM
OT  - Cobimetinib
OT  - Dabrafenib
OT  - Indirect treatment comparison
OT  - Metastatic melanoma
OT  - Trametinib
OT  - Vemurafenib
EDAT- 2017/01/06 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/01/04
CRDT- 2017/01/06 06:00
PHST- 2016/08/13 00:00 [received]
PHST- 2016/12/06 00:00 [accepted]
PHST- 2017/01/06 06:00 [entrez]
PHST- 2017/01/06 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/01/04 00:00 [pmc-release]
AID - 10.1186/s13045-016-0369-8 [pii]
AID - 369 [pii]
AID - 10.1186/s13045-016-0369-8 [doi]
PST - epublish
SO  - J Hematol Oncol. 2017 Jan 4;10(1):3. doi: 10.1186/s13045-016-0369-8.