PMID- 27581207
OWN - NLM
STAT- MEDLINE
DCOM- 20171107
LR  - 20181113
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 11
IP  - 1
DP  - 2016 Sep 1
TI  - Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus 
      syndrome: pooled analysis of two trials.
PG  - 120
LID - 10.1186/s13023-016-0506-z [doi]
LID - 120
AB  - BACKGROUND: Aberrant activation of the Hedgehog (Hh) pathway is a key driver in 
      the pathogenesis of basal cell carcinomas (BCCs), including patients with BCC 
      nevus syndrome (BCCNS). It is unclear whether BCCs arising in patients with BCCNS 
      respond differently to vismodegib than in patients without BCCNS. We examined the 
      best overall response rate (BORR) and adverse events (AEs) of vismodegib in 
      patients with advanced BCC (aBCC) with and without BCCNS. METHODS: Patients were 
      treated with vismodegib 150 mg/day in the ERIVANCE BCC trial (ClinicalTrials.gov 
      number, NCT00833417) and the expanded access study (EAS; ClinicalTrials.gov 
      number, NCT01160250). BCCNS diagnosis was based on medical history at the time of 
      enrollment. Metastatic BCC response was evaluated using Response Evaluation 
      Criteria In Solid Tumors, version 1.0 (RECIST v1.0) in both studies. Locally 
      advanced BCC was evaluated by a novel composite end point in ERIVANCE BCC and by 
      RECIST v1.0 in the EAS. Response assessments were performed every 8 weeks in 
      ERIVANCE BCC and every 8-16 weeks in the EAS. Safety assessments (National Cancer 
      Institute Common Terminology Criteria for Adverse Events, version 3.0) were 
      performed monthly in both trials. Because of described differences in response 
      assessment/schedule, patients with BCCNS were not pooled across trials. Analytic 
      cohorts for BCCNS and sporadic aBCC were created within each trial for comparison 
      using descriptive statistical methods. RESULTS: Forty-one patients with BCCNS 
      were included in the study: 22 from ERIVANCE BCC and 19 from the EAS. 
      Investigator-assessed BORR in BCCNS groups ranged from 31 to 81 % in patients 
      with locally advanced BCC (n = 33) and was 50 % in patients with metastatic BCC 
      (n = 6). These results were comparable with the non-BCCNS groups. Incidence and 
      severity of AEs were also comparable between the BCCNS and non-BCCNS groups. 
      Amenorrhea was observed in both patient cohorts and was reversible in two 
      patients who discontinued treatment. CONCLUSION: Vismodegib demonstrated 
      comparable efficacy and safety against aBCC in patients with and without BCCNS.
FAU - Chang, Anne Lynn S
AU  - Chang AL
AD  - Stanford University, 450 Broadway, Pavilion C, 2nd floor, Redwood City, CA, 
      94063, USA. alschang@stanford.edu.
FAU - Arron, Sarah T
AU  - Arron ST
AD  - University of California, San Francisco, 1701 Divisadero Street, Box 0316, San 
      Francisco, CA, 94115, USA.
FAU - Migden, Michael R
AU  - Migden MR
AD  - The University of Texas MD Anderson Cancer Center, Unit 1452, 1400 Pressler 
      Street, Houston, TX, 77030, USA.
FAU - Solomon, James A
AU  - Solomon JA
AD  - Ameriderm Research, 725 West Granada Boulevard, Suite 44, Ormond Beach, FL, 
      32174, USA.
AD  - University of Central Florida, CI6850 Lake Nona Boulevard, Orlando, FL, 32827, 
      USA.
AD  - University of Illinois, 506 South Mathews Avenue, Urbana, IL, 61801, USA.
FAU - Yoo, Simon
AU  - Yoo S
AD  - Northwestern University, 676 North St. Clair Street, Suite 1600, Chicago, IL, 
      60611, USA.
FAU - Day, Bann-Mo
AU  - Day BM
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
FAU - McKenna, Edward F
AU  - McKenna EF
AD  - Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
FAU - Sekulic, Aleksandar
AU  - Sekulic A
AD  - Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00833417
SI  - ClinicalTrials.gov/NCT01160250
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20160901
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (HhAntag691)
RN  - 0 (Pyridines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anilides/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Carcinoma, Basal Cell/*drug therapy
MH  - Female
MH  - Hedgehog Proteins/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyridines/adverse effects/*therapeutic use
MH  - Skin Neoplasms/drug therapy
MH  - Young Adult
PMC - PMC5007799
OTO - NOTNLM
OT  - Basal cell carcinoma
OT  - Basal cell carcinoma nevus syndrome
OT  - Vismodegib
EDAT- 2016/09/02 06:00
MHDA- 2017/11/08 06:00
PMCR- 2016/09/01
CRDT- 2016/09/02 06:00
PHST- 2016/04/08 00:00 [received]
PHST- 2016/08/23 00:00 [accepted]
PHST- 2016/09/02 06:00 [entrez]
PHST- 2016/09/02 06:00 [pubmed]
PHST- 2017/11/08 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - 10.1186/s13023-016-0506-z [pii]
AID - 506 [pii]
AID - 10.1186/s13023-016-0506-z [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2016 Sep 1;11(1):120. doi: 10.1186/s13023-016-0506-z.