‘Breakthrough’ Approach to Advanced Basal Cell Carcinoma via Inhibition of Hedgehog Pathway

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The first-in-class Hedgehog pathway inhibitor vismodegib appears to be a successful treatment for advanced basal cell carcinoma, a disfiguring and debilitating disease, according to a pivotal multicenter nonrandomized trial presented as a Best Abstract at a Presidential Session during the recent European Multidisciplinary Cancer Congress in Stockholm.1 At present, there is no standard of care for the small minority of basal cell cancers that present as locally advanced or metastatic.

2.17.49_dirix.jpg“This is an unmet need. Our study shows substantial benefit for advanced basal cell carcinoma with this new approach using a Hedgehog pathway inhibitor,” said Luc Dirix, MD, Sint-Augustinus Hospital, Antwerp, Belgium.

The data from the study were compelling, but perhaps more compelling were the photos of faces of patients with widespread ulcerated lesions of the face and head that resolved with treatment.

“It is hard to appreciate, unless you have seen the photos, how remarkable these results really are,” stated Sandra Horning, MD, Head of Clinical Development in Hematology/Oncology for Genentech, speaking to reporters at a press conference.

Data Breakdown

The study population included 99 patients—33 with metastatic disease and 63 with locally advanced disease. Treatment was with 150 mg/d of oral vismodegib until disease progression, unacceptable toxicity, or withdrawal from the study. The median age of patients was 62, and 100% were white. Overall, 38% of patients’ lesions were inoperable, and 62% were not surgical candidates.

2.17.49_chart.jpgAmong the group with metastatic basal cell cancer, overall response rate was 30%, and stable disease was observed in 63%. For those with locally advanced basal cell carcinoma, overall response rate was 43% and stable disease was observed in 40%. Median progression-free survival at 10 months was identical in the two groups. Absence of basal cell cancer on biopsy was reported in 54% of the cohort with locally advanced disease.

Few serious adverse events were attributed to vismodegib. Of 26 (25%) serious adverse events, 4 (4%) were deemed drug-related. “The common adverse events were predominantly mild to moderate and related to inhibition of the Hedgehog pathway, such as muscle spasms, alopecia, taste disturbance, weight loss, and fatigue,” he told listeners. ■

Disclosure: Dr. Horning is Senior Vice President, Global Head of Clinical Development Hematology/Oncology for Genentech. Dr. Dirix reported no potential conflicts of interest.

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


1. Dirix L, Migden MR, Oro AR, et al: A pivotal multicenter trial evaluating efficacy and safety of the Hedgehog pathway inhibitor vismodegib in patients with advanced basal cell carcinoma. European Multidisciplinary Cancer Congress. Abstract 1BA. Presented September 24, 2011.

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