PMID- 23918947
OWN - NLM
STAT- MEDLINE
DCOM- 20131122
LR  - 20220321
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 26
DP  - 2013 Sep 10
TI  - Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in 
      patients with metastatic melanoma.
PG  - 3205-11
LID - 10.1200/JCO.2013.49.8691 [doi]
AB  - PURPOSE: Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. 
      Our multicenter, single-arm, phase II study assessed the safety and clinical 
      activity of dabrafenib in BRAF(V600E/K) mutation-positive metastatic melanoma 
      (mut(+) MM). PATIENTS AND METHODS: Histologically confirmed patients with stage 
      IV BRAF(V600E/K) mut(+) MM received oral dabrafenib 150 mg twice daily until 
      disease progression, death, or unacceptable adverse events (AEs). The primary end 
      point was investigator-assessed overall response rate in BRAF(V600E) mut(+) MM 
      patients. Secondary end points included progression-free survival (PFS) and 
      overall survival (OS). Exploratory objectives included the comparison of BRAF 
      mutation status between tumor-specific circulating cell-free DNA (cfDNA) and 
      tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome. 
      RESULTS: Seventy-six patients with BRAF(V600E) and 16 patients with BRAF(V600K) 
      mut(+) MM were enrolled onto the study. In the BRAF(V600E) group, 45 patients 
      (59%) had a confirmed response (95% CI, 48.2 to 70.3), including five patients 
      (7%) with complete responses. Two patients (13%) with BRAF(V600K) mut(+) MM had a 
      confirmed partial response (95% CI, 0 to 28.7). In the BRAF(V600E) and 
      BRAF(V600K) groups, median PFS was 6.3 months and 4.5 months, and median OS was 
      13.1 months and 12.9 months, respectively. The most common AEs were arthralgia 
      (33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 25 patients (27%) 
      experienced a serious AE and nine patients (10%) had squamous cell carcinoma. 
      Baseline cfDNA levels predicted response rate and PFS in BRAF(V600E) mut(+) MM 
      patients. CONCLUSION: Dabrafenib was well tolerated and clinically active in 
      patients with BRAF(V600E/K) mut(+) MM. cfDNA may be a useful prognostic and 
      response marker in future studies.
FAU - Ascierto, Paolo A
AU  - Ascierto PA
AD  - Paolo A. Ascierto, Ester Simeone, Instituto Nazionale Tumori Fondazione "G. 
      Pascale," Napoli, Italy; David Minor, California Pacific Center for Melanoma 
      Research and Treatment, San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer 
      Center, University of California, Los Angeles; Omid Hamid, Experimental 
      Therapeutics/Immunotherapy, The Angeles Clinic and Research Institute, Los 
      Angeles, CA; Anne O'Hagan, Niki Arya, Mary Guckert, Anne-Marie Martin, Jolly 
      Mazumdar, Vicki L. Goodman, GlaxoSmithKline Oncology, Collegeville; Ravi 
      Amaravadi, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; 
      Kevin B. Kim, The University of Texas MD Anderson Cancer Center, Houston, TX; 
      Celeste Lebbe, Assistance Publique-Hopitaux de Paris, Hopital Saint Louis, Paris, 
      Universite Paris Diderot, Paris; Jean-Jacques Grob, Aix-Marseille University, 
      Assistance Publique-Hopitaux de Marseille, Hopital Timone, Marseille, France; 
      Dirk Schadendorf, University Hospital Essen, Essen; Tabea Wilhelm, Uwe Trefzer, 
      Charite-Universitatsmedizin, Berlin, Germany; Richard F. Kefford, Georgina V. 
      Long, Westmead Hospital and Melanoma Institute Australia, University of Sydney, 
      Sydney, Australia.
FAU - Minor, David
AU  - Minor D
FAU - Ribas, Antoni
AU  - Ribas A
FAU - Lebbe, Celeste
AU  - Lebbe C
FAU - O'Hagan, Anne
AU  - O'Hagan A
FAU - Arya, Niki
AU  - Arya N
FAU - Guckert, Mary
AU  - Guckert M
FAU - Schadendorf, Dirk
AU  - Schadendorf D
FAU - Kefford, Richard F
AU  - Kefford RF
FAU - Grob, Jean-Jacques
AU  - Grob JJ
FAU - Hamid, Omid
AU  - Hamid O
FAU - Amaravadi, Ravi
AU  - Amaravadi R
FAU - Simeone, Ester
AU  - Simeone E
FAU - Wilhelm, Tabea
AU  - Wilhelm T
FAU - Kim, Kevin B
AU  - Kim KB
FAU - Long, Georgina V
AU  - Long GV
FAU - Martin, Anne-Marie
AU  - Martin AM
FAU - Mazumdar, Jolly
AU  - Mazumdar J
FAU - Goodman, Vicki L
AU  - Goodman VL
FAU - Trefzer, Uwe
AU  - Trefzer U
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20130805
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Imidazoles)
RN  - 0 (Oximes)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - QGP4HA4G1B (dabrafenib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain Neoplasms/*drug therapy/mortality/secondary
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Imidazoles/*therapeutic use
MH  - International Agencies
MH  - Male
MH  - Melanoma/*drug therapy/mortality/pathology
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Oximes/*therapeutic use
MH  - Prognosis
MH  - Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/genetics
MH  - Survival Rate
MH  - Young Adult
EDAT- 2013/08/07 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/08/07 06:00
PHST- 2013/08/07 06:00 [entrez]
PHST- 2013/08/07 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - JCO.2013.49.8691 [pii]
AID - 10.1200/JCO.2013.49.8691 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Sep 10;31(26):3205-11. doi: 10.1200/JCO.2013.49.8691. Epub 
      2013 Aug 5.