Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib - 18/12/13
, James A. Solomon, MD, PhD b, c, d, John D. Hainsworth, MD e, Leonard Goldberg, MD f, Edward McKenna, PharmD, BCOP g, Bann-mo Day, PhD g, Diana M. Chen, MD g, Glen J. Weiss, MD hAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : basal cell carcinoma, basal cell nevus syndrome, expanded access, Hedgehog pathway inhibitor, locally advanced, metastatic, vismodegib
Abbreviations used : AE, BCC, BCNS, ECOG, FDA, ORR, RECIST, SMO, TEAE
Plan
| Funded by Roche-Genentech. Medical writing assistance was provided by Saema Magre, PhD, and Tony Serino, PhD, at ApotheCom and funded by F. Hoffmann-La Roche. |
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| Disclosure: Dr Chang has received honoraria for participation on an advisory board for Genentech and has served as an investigator and received grants from Genentech and Novartis. Dr Solomon has received honoraria for participation on an advisory board for Genentech, and his institution has received grants from Genentech. Drs McKenna, Day, and Chen are salaried employees of and have received stock options from Genentech. Dr Weiss has served as an investigator for Infinity Pharma, Genentech, and Eli Lilly (no compensation received); has received honoraria as a speaker for Genentech, Quintiles, Medscape, Pfizer, and Eli Lilly; and his institution has received funds from Infinity Pharma, Genentech, and Eli Lilly for conducting clinical trials. Drs Hainsworth and Goldberg have no conflicts of interest to declare. |
Vol 70 - N° 1
P. 60-69 - janvier 2014 Retour au numéro
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