Vismodegib Provides a Novel Treatment for Advanced Basal Cell Carcinoma


Objective: To review and evaluate vismodegib, the first US Food and Drug Administration (FDA) approved treatment for locally advanced (laBCC) or metastatic basal cell carcinoma (mBCC) that has recurred after surgery or for patients in which surgery or radiation is not an option. Data Sources: A literature search using PubMed was conducted through January 2013, using the terms vismodegib, GDC-0449, and Erivedge. Additional literature was found through the reference citations of identified articles. Study Selection and Data Extraction: Potential sources were limited to human studies published in English with a priority placed on those focused on laBCC or mBCC. Data Synthesis: Vismodegib is a selective inhibitor of the hedgehog (Hh) pathway approved for the treatment of laBCC or mBCC that has recurred after surgery, or for patients for whom surgery or radiation is contraindicated. Vismodegib inhibits cancer cell growth and survival by binding Smoothened, a transmembrane protein involved in the Hedgehog signal transduction. Vismodegib is administered orally at a dose of 150 mg daily. It is primarily eliminated through the feces unchanged but does have some oxidative metabolites produced from the recombinant cytochrome P450 (CYP) 2C9 and CYP3A4/5. Despite CYP450 involvement, it appears to have very few drug interactions. The most common adverse events reported with vismodegib include muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, anorexia, and diarrhea. FDA approval was based on a single arm phase II study that demonstrated an objective response rate of 30% in mBCC patients and 45% in laBCC patients. Vismodegib was approved by the FDA on January 30, 2012 for use in patients with advanced basal cell carcinoma, and continues to be studied in other patient populations for additional potential uses. Conclusions: Based on a review of current evidence, vismodegib provides an effective and well-tolerated treatment for otherwise untreatable basal cell carcinoma.

Share and Cite:

J. Kelm, T. Magliaro, M. Anderson and C. Mach, "Vismodegib Provides a Novel Treatment for Advanced Basal Cell Carcinoma," Journal of Cancer Therapy, Vol. 5 No. 2, 2014, pp. 217-221. doi: 10.4236/jct.2014.52027.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. N. Amaria, D. W. Bowles, K. D. Lewis and A. Jimeno, “Vismodegib in Basal Cell Carcinoma,” Drugs Today (Barc), Vol. 48, No. 7, 2012, pp .459-467.
[2] M. Guha, “Hedgehog Inhibitor Gets Landmark Skin Cancer Approval, But Questions Remain for Wider Potential,” Nature Reviews Drug Discovery, Vol. 11, No. 4, 2012, pp. 257-258. 1038/nrd3714
[3] F. Cirrone and C. S. Harris, “Vismodegib and the Hedgehog Pathway: A New Treatment for Basal Cell Carcinoma,” Clinical Therapeutics, Vol. 34, No. 10, 2012, pp. 2039-2050. j.clinthera.2012.08.011
[4] US Food and Drug Administration, “FDA Approves New Treatment for Most Common Type of Skin Cancer,” 2012.
[5] C. Fellner, “Vismodegib (Erivedge) for Advanced Basal Cell Carcinoma,” P T, Vol. 37, No. 12, 2012, pp. 670-682.
[6] K. A. Lyseng-Williamson and G. M. Keating, “Vismodegib: A Guide to Its Use in Locally Advanced or Metastatic Basal Cell Carcinoma,” American Journal of Clinical Dermatology, Vol. 14, No. 1, 2013, pp. 61-64.
[7] A. A. Dlugoszand M. Talpaz, “Following the Hedgehog to New Cancer Therapies,” The New England Journal of Medicine, Vol. 361, No. 12, 2009, pp. 1202-1205.
[8] S. H. Amin, R. Tibes, J. Kim and C. P. Hybarger, “Hedgehog Antagonist GDC-0449 Is Effective in the Treatment of Advanced Basal Cell Carcinoma,” Laryngoscope, Vol. 120, No. 12, 2010, pp. 2456-2459.
[9] P. M. LoRusso, C. M. Rudin, J. C. Reddy, R. Tibes, G. J. Weiss, M. J. Borad, et al., “Phase I Trial of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Refractory, Locally Advanced or Metastatic Solid Tumors,” Clinical Cancer Research, Vol. 17, No. 8, 2011, pp. 2502-2511.
[10] P. M. Lorusso, A. Jimeno, G. Dy, A. Adjei, J. Berlin, L. Leichman, et al., “Pharmacokinetic Dose-Scheduling Study of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Locally Advanced or Metastatic Solid Tumors,” Clinical Cancer Research, Vol. 17, No. 17, 2011, pp. 5774-5782.
[11] Product Information. Erivedge (Vismodegib). San Francisco, Genentech, Inc., 2012.
[12] R. A. Graham, C. E. Hop, M. T. Borin, B. L. Lum, D. Colburn, I. Chang, et al., “Single and Multiple Dose Intravenous and Oral Pharmacokinetics of the Hedgehog Pathway Inhibitor Vismodegib in Healthy Female Subjects,” British Journal of Clinical Pharmacology, Vol. 74, No. 5, 2012, pp. 788-796.
[13] D. D. Von Hoff, P. M. LoRusso, C. M. Rudin, J. C. Reddy, Yauch RL, Tibes R, et al., “Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 361 No. 12, 2009, pp. 1164-1172.
[14] A. Sekulic, M. R. Migden, A. E. Oro, L. Dirix, K. D. Lewis, J. D. Hainsworth, et al., “Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 366, No. 23, 2012, pp. 2171-2179.
[15] M. Allison, “Hedgehog Hopes Lifted by Approval... and Stung by Failure,” Nature Biotechnology, Vol. 30, No. 3, 2012, p. 203.
[16] S. B. Kaye, L. Fehrenbacher, R. Holloway, A. Amit, B. Karlan, B. Slomovitz, et al., “A phase II, Randomized, Placebo-Controlled Study of Vismodegib as Maintenance Therapy in Patients with Ovarian Cancer in Second or Third Complete Remission,” Clinical Cancer Research, Vol. 18, No. 23, 2012, pp. 6509-6518.
[17] J. Berlin, J. C. Bendell, L. L. Hart, I. Firdaus, I. Gore, R. C. Hermann, et al., “A Randomized Phase II Trial of Vismodegib versus Placebo with FOLFOX or FOLFIRI and Bevacizumab in Patients with Previously Untreated Metastatic Colorectal Cancer,” Clinical Cancer Research, Vol. 19, No. 1, 2013, pp. 258-267.
[18] J. Y. Tang, J. M. Mackay-Wiggan, M. Aszterbaum, R. L. Yauch, J. Lindgren, K. Chang, et al., “Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome,” The New England Journal of Medicine, Vol. 366, No. 23, 2012, pp. 2180-2188.
[19] D. A. Hussar and S. P. Eckel, “Ivacaftor, Vismodegib, and Ingenol Mebutate,” Journal of American Pharmacists Association, Vol. 52, No. 3, 2012, pp. 418-422. 12517
[20] J. A. Low and F. J. de Sauvage, “Clinical Experience with Hedgehog Pathway Inhibitors,” Journal of Clinical Oncology, Vol. 28, No. 26, 2010, pp. 5321-5316.
[21] P. M. LoRusso, S. A. Piha-Paul, M. Mita, A. D. Colevas, V. Malhi, D. Colburn, et al., “Co-Administration of Vismodegib with Rosiglitazone or Combined Oral Contraceptive in Patients with Locally Advanced or Metastatic Solid Tumors: A Pharmacokinetic Assessment of Drug-Drug Interaction Potential,” Cancer Chemother Pharmacol, Vol. 71, No. 1, 2013, pp. 193-202.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.