title: Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Vismodegib demonstrated comparable efficacy and safety against aBCC in patients with and without BCCNS.
authors: Stanford University, 450 Broadway, Pavilion C, 2nd floor, Redwood City, CA, 94063, USA. alschang@stanford.edu.
authors: Anne Lynn S
authors: AL
authors: Chang
authors: University of California, San Francisco, 1701 Divisadero Street, Box 0316, San Francisco, CA, 94115, USA.
authors: Sarah T
authors: ST
authors: Arron
authors: The University of Texas MD Anderson Cancer Center, Unit 1452, 1400 Pressler Street, Houston, TX, 77030, USA.
authors: Michael R
authors: MR
authors: Migden
authors: Ameriderm Research, 725 West Granada Boulevard, Suite 44, Ormond Beach, FL, 32174, USA.|University of Central Florida, CI6850 Lake Nona Boulevard, Orlando, FL, 32827, USA.|University of Illinois, 506 South Mathews Avenue, Urbana, IL, 61801, USA.
authors: James A
authors: JA
authors: Solomon
authors: Northwestern University, 676 North St. Clair Street, Suite 1600, Chicago, IL, 60611, USA.
authors: Simon
authors: S
authors: Yoo
authors: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
authors: Bann-Mo
authors: BM
authors: Day
authors: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
authors: Edward F
authors: EF
authors: McKenna
authors: Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors: Aleksandar
authors: A
authors: Sekulic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines
keywords: Basal cell carcinoma; Basal cell carcinoma nevus syndrome; Vismodegib