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Vismodegib showed adverse events in effectively treating patients with basal cell nevus syndrome
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Jean Y. Tang
Vismodegib, an orally administered hedgehog-pathway inhibitor, reduced the new formation and the size of existing basal cell carcinomas in patients with basal cell nevus syndrome but also triggered adverse events, according to study results.
Jean Y. Tang, MD, PhD, an assistant professor of dermatology at Stanford School of Medicine, and colleagues conducted the randomized, double blind, placebo-controlled trial of patients with basal cell nevus syndrome to test the efficacy of vismodegib (Erivedge, Genentech) as an alternative to surgery. The trial included 41 patients, each of whom had at least 10 surgically eligible basal cell carcinomas at study entry or removed during the previous 2 years.
Twenty-six patients were administered vismodegib 150 mg daily and 15 patients received placebo for a planned 18 months. The primary endpoint was reduction in new surgically eligible basal cell carcinomas with vismodegib vs. placebo after 3 months. The secondary endpoint was reduction in the size of existing basal cell carcinomas.
After a mean follow-up of 8 months, patients assigned to vismodegib had significantly reduced new basal cell carcinomas compared with patients assigned to placebo (two vs. 29 per year; P<.0001). Vismodegib also reduced the size of existing surgically eligible basal cell carcinomas by an average of –65%, compared with –11% among patients assigned to placebo (P=.003).
Grade-1/grade-2 adverse events reported by patients in the vismodegib arm included dysgeusia, loss of weight and hair, and muscle cramps. Fourteen patients (54%) in the vismodegib arm discontinued treatment due to adverse events.
Researchers also determined through basal cell carcinoma biopsies that after 1 month, hedgehog target-gene expression in GLI1 messenger RNA was reduced by 90% in patients assigned to vismodegib (P<.001). Tumor proliferation was significantly reduced, but apoptosis remained unaffected.
“Overall, our findings confirm the essential role of the hedgehog pathway in basal cell carcinomas and indicate that vismodegib is efficacious in preventing and treating basal cell carcinomas in patients with the basal cell nevus syndrome,” the researchers concluded. “The high rate of discontinuing the drug … is unlikely to be ameliorated by altering the chemical structure.”
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Tang JY. N Engl J Med. 2012;366:2180-2188.
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