Anne Lynn S Chang1, James A Solomon2, John D Hainsworth3, Leonard Goldberg4, Edward McKenna5, Bann-mo Day5, Diana M Chen5, Glen J Weiss6. 1. Stanford University School of Medicine, Stanford, California. Electronic address: alschang@stanford.edu. 2. Ameriderm Research, Ormond Beach, Florida; Sarah Cannon Research Institute, Nashville, Tennessee; University of Illinois, Urbana Champaign, College of Medicine, Urbana, Illinois. 3. University of Central Florida, College of Medicine, Orlando, Florida. 4. Dermsurgery Associates, Houston, Texas. 5. Genentech Inc, South San Francisco, California. 6. Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, Scottsdale, Arizona.
Abstract
BACKGROUND: Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib. OBJECTIVE: We sought to assess efficacy and safety of vismodegib, while providing early drug access to patients with advanced BCC and limited treatment options. METHODS: This was an open-label, multicenter study in patients with advanced BCC inappropriate for radiotherapy or surgery. Patients received 150 mg vismodegib daily until disease progression or intolerable toxicity. Tumor response was assessed via Response Evaluation Criteria in Solid Tumors version 1.0. RESULTS: A total of 119 patients with advanced BCC took vismodegib for a median of 5.5 months. Objective responses occurred in 46.4% of locally advanced BCC and 30.8% of patients with metastatic BCC. Response was negatively associated with prior systemic therapy in patients with locally advanced BCC (P = .002). Mean follow-up for safety was 6.5 months, with muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) as the most common adverse events. LIMITATIONS: Abbreviated follow-up time because of study termination upon FDA approval was a limitation. CONCLUSION: This study provides important clinical data supporting the efficacy and safety of vismodegib. Larger studies are underway to assess predictors of response and long-term outcomes.
BACKGROUND: Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib. OBJECTIVE: We sought to assess efficacy and safety of vismodegib, while providing early drug access to patients with advanced BCC and limited treatment options. METHODS: This was an open-label, multicenter study in patients with advanced BCC inappropriate for radiotherapy or surgery. Patients received 150 mg vismodegib daily until disease progression or intolerable toxicity. Tumor response was assessed via Response Evaluation Criteria in Solid Tumors version 1.0. RESULTS: A total of 119 patients with advanced BCC took vismodegib for a median of 5.5 months. Objective responses occurred in 46.4% of locally advanced BCC and 30.8% of patients with metastatic BCC. Response was negatively associated with prior systemic therapy in patients with locally advanced BCC (P = .002). Mean follow-up for safety was 6.5 months, with muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) as the most common adverse events. LIMITATIONS: Abbreviated follow-up time because of study termination upon FDA approval was a limitation. CONCLUSION: This study provides important clinical data supporting the efficacy and safety of vismodegib. Larger studies are underway to assess predictors of response and long-term outcomes.
Authors: Priyadharsini Nagarajan; Maryam M Asgari; Adele C Green; Samantha M Guhan; Sarah T Arron; Charlotte M Proby; Dana E Rollison; Catherine A Harwood; Amanda Ewart Toland Journal: Clin Cancer Res Date: 2018-12-06 Impact factor: 12.531
Authors: Rachelle W Johnson; Alyssa R Merkel; Jonathan M Page; Nazanin S Ruppender; Scott A Guelcher; Julie A Sterling Journal: Clin Exp Metastasis Date: 2014-10-31 Impact factor: 5.150
Authors: Marie Le Moigne; Mélanie Saint-Jean; Adam Jirka; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Aurélie Gaultier; Amir Khammari; Dominique Darmaun; Brigitte Dréno Journal: Support Care Cancer Date: 2015-09-29 Impact factor: 3.603