Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:70

Article

Chang, Anne Lynn S.¹  Solomon, James A.^2,3,4  Hainsworth, John D.⁵  Goldberg, Leonard⁶  McKenna, Edward⁷  Day, Bann-mo⁷  Chen, Diana M.⁷  Weiss, Glen J.⁸ 

[1] Stanford Univ, Sch Med, Stanford, CA USA

[2] Ameriderm Res, Ormond Beach, FL USA

[3] Sarah Cannon Res Inst, Nashville, TN USA

[4] Univ Illinois, Coll Med, Urbana, IL 61801 USA

[5] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA

[6] Dermsurg Associates, Houston, TX USA

[7] Genentech Inc, San Francisco, CA 94080 USA

[8] Scottsdale Healthcare, Virginia G Piper Canc Ctr Clin Trials, Scottsdale, AZ USA

关键词: basal cell carcinoma;    basal cell nevus syndrome;    expanded access;    Hedgehog pathway inhibitor;    locally advanced;    metastatic;    vismodegib;   

DOI  :  10.1016/j.jaad.2013.09.012

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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