Expert Point of View: ‘Breakthrough’ Approach to Advanced Basal Cell Carcinoma via Inhibition of Hedgehog Pathway

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2.17.49_robert.jpg“Vismodegib is a breakthrough for advanced basal cell carcinoma. These responses were convincing and spectacular, with a clinical benefit in more than 80% of patients and progression-free survival of 10 months,” said Caroline Robert, MD, Institut Gustav Roussy, Villejuif Paris-Sud, France, who was formal discussant for the paper by Dirix et al at the European Multidisciplinary Cancer Congress.

Basal cell cancer, though common, is usually a slow-growing cancer. “Despite this, we still see some patients with extensive advanced disease,” she said.

Phase II Trial

Patients with Gorlin syndrome are “covered” with endless basal cell cancers, she continued. “Interim results of a phase II study of 41 patients with Gorlin syndrome showed a good clinical response with vismodegib, with almost no new tumor growth,” Dr. Robert told the audience.1 Despite the good clinical response, and the fact that serious adverse events are rare with this drug, long-term tolerance may be problematic, because 40% of the patients with Gorlin syndrome eventually stopped therapy in that trial.

“We need to continue to find treatment modalities that avoid side effects in high-risk patients,” Dr. Robert stated.

There may be a role for neoadjuvant vismodegib, she suggested, and surgery should remain in the treatment algorithm. The Hedgehog pathway is involved in stromal cell biology and angiogenesis, and the role of vismodegib should be explored in other tumors. It is presently being tested in pancreatic cancer and chondrosarcoma. ■

Disclosure: Dr. Robert is a consultant for Roche, GlaxoSmithKline, and Bristol-Myers Squibb.


1. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al: An investigator-initiated, phase II randomized, double-blind, placebo-controlled trial of GDC-0449 for prevention of BCCs in basal cell nevus syndrome (BCNS) patients. American Association for Cancer Research 102nd Annual Meeting, Abstract LB-1. Presented April 3, 2011.

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