PMID- 27532019
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160817
LR  - 20210102
IS  - 2051-1426 (Print)
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 4
DP  - 2016
TI  - Phase II study of vemurafenib followed by ipilimumab in patients with previously 
      untreated BRAF-mutated metastatic melanoma.
PG  - 44
LID - 10.1186/s40425-016-0148-7 [doi]
LID - 44
AB  - BACKGROUND: Ipilimumab (IPI), an anti-CTLA-4 antibody, and vemurafenib (VEM), a 
      BRAF inhibitor, have distinct mechanisms of action and shared toxicities (e.g., 
      skin, gastrointestinal [GI] and hepatobiliary disorders) that may preclude 
      concomitant administration. Concurrent administration of IPI and VEM previously 
      showed significant dose-limiting hepatotoxicity in advanced melanoma. This 
      single-arm, open-label, phase II study evaluated a sequencing strategy with these 
      two agents in previously untreated patients with BRAF-mutated advanced melanoma. 
      METHODS: This study was divided into two parts. During Part 1 (VEM1-IPI), 
      patients received VEM 960 mg twice daily for 6 weeks followed by IPI 10 mg/kg 
      every 3 weeks for 4 doses (induction), then every 12 weeks (maintenance) 
      beginning at week 24 until disease progression or unacceptable toxicity. During 
      Part 2 (VEM2), patients who progressed after IPI received VEM at their previously 
      tolerated dose. The primary objective was to estimate the incidence of grade 3/4 
      drug-related skin adverse events (AEs) during VEM1-IPI. RESULTS: All patients who 
      were initially treated with VEM (n = 46) received IPI induction therapy; 8 
      received IPI maintenance and 19 were treated during VEM2. During VEM1-IPI, the 
      incidence of grade 3/4 drug-related AEs associated with the skin, GI tract, and 
      hepatobiliary system was 32.6 %, 21.7 %, and 4.3 %, respectively. There were no 
      drug-related deaths. At a median follow-up of 15.3 months, median overall 
      survival was 18.5 months. Median progression-free survival was 4.5 months. 
      CONCLUSIONS: VEM (960 mg twice daily for 6 weeks) followed by IPI 10 mg/kg has a 
      manageable safety profile. The benefits/risks of BRAF inhibitors followed by 
      immunotherapy should be evaluated further in light of continuing developments in 
      treatment options for metastatic melanoma. TRIAL REGISTRATION: ClinicalTrials.gov 
      identifier: NCT01673854 (CA184-240) Registered 24 August 2012.
FAU - Amin, Asim
AU  - Amin A
AD  - Levine Cancer Institute, Carolinas Healthcare System, Medical Oncology, 1021 
      Morehead Medical Drive, Charlotte, NC 28204 USA.
FAU - Lawson, David H
AU  - Lawson DH
AD  - Winship Cancer Institute of Emory University, Atlanta, GA USA.
FAU - Salama, April K S
AU  - Salama AK
AD  - Duke Cancer Institute, Durham, NC USA.
FAU - Koon, Henry B
AU  - Koon HB
AD  - Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 
      USA.
FAU - Guthrie, Troy Jr
AU  - Guthrie T Jr
AD  - Baptist Cancer Institute, Jacksonville, FL USA.
FAU - Thomas, Sajeve S
AU  - Thomas SS
AD  - MD Anderson Cancer Center Orlando, Orlando, FL USA.
FAU - O'Day, Steven J
AU  - O'Day SJ
AD  - John Wayne Cancer Institute at Providence Saint John's Health Center, Santa 
      Monica, CA USA.
FAU - Shaheen, Montaser F
AU  - Shaheen MF
AD  - University of New Mexico Cancer Center, Albuquerque, NM USA.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Bristol-Myers Squibb, Princeton, NJ USA ; Current Address: KBP BioSciences, 
      Princeton, NJ USA.
FAU - Francis, Stephen
AU  - Francis S
AD  - Bristol-Myers Squibb, Princeton, NJ USA.
FAU - Hodi, F Stephen
AU  - Hodi FS
AD  - Dana-Farber Cancer Institute, Boston, MA USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01673854
PT  - Journal Article
DEP - 20160816
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
PMC - PMC4986368
OTO - NOTNLM
OT  - BRAF inhibitor
OT  - CTLA-4
OT  - Immune checkpoint inhibitor
OT  - Immunotherapy
OT  - Ipilimumab
OT  - Melanoma
OT  - Targeted agent
OT  - Vemurafenib
EDAT- 2016/08/18 06:00
MHDA- 2016/08/18 06:01
PMCR- 2016/08/16
CRDT- 2016/08/18 06:00
PHST- 2016/05/20 00:00 [received]
PHST- 2016/07/11 00:00 [accepted]
PHST- 2016/08/18 06:00 [entrez]
PHST- 2016/08/18 06:00 [pubmed]
PHST- 2016/08/18 06:01 [medline]
PHST- 2016/08/16 00:00 [pmc-release]
AID - 148 [pii]
AID - 10.1186/s40425-016-0148-7 [doi]
PST - epublish
SO  - J Immunother Cancer. 2016 Aug 16;4:44. doi: 10.1186/s40425-016-0148-7. 
      eCollection 2016.