Title

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

Authors

Authors

A. L. S. Chang; J. A. Solomon; J. D. Hainsworth; L. Goldberg; E. McKenna; B. M. Day; D. M. Chen;G. J. Weiss

Comments

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Abbreviated Journal Title

J. Am. Acad. Dermatol.

Keywords

basal cell carcinoma; basal cell nevus syndrome; expanded access; Hedgehog pathway inhibitor; locally advanced; metastatic; vismodegib; SIGNALING PATHWAY; SKIN-CANCER; GUIDELINES; MANAGEMENT; MUTATIONS; TUMORS; Dermatology

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.

Journal Title

Journal of the American Academy of Dermatology

Volume

70

Issue/Number

1

Publication Date

1-1-2014

Document Type

Article

Language

English

First Page

60

Last Page

69

WOS Identifier

WOS:000328694200015

ISSN

0190-9622

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