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 recent study results.
In a randomized, double blind, placebo-controlled trial of patients with basal cell nevus syndrome, researchers sought to test the efficacy of vismodegib (Erivedge, Genentech-Curis) as an option to surgery. The trial included 41 patients who each had at least 10 surgically eligible basal cell carcinomas at study entry or removed during the previous 2 years. Twenty-six patients were administered 150 mg oral vismodegib daily and 15 received placebo for a planned 18 months. Primary endpoint was reduction in new surgically eligible basal cell carcinomas with vismodegib vs. placebo after 3 months; secondary endpoint was reduction in the size of existing basal cell carcinomas.
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After a mean follow-up of 8 months, patients taking vismodegib significantly reduced new basal cell carcinomas compared with patients taking placebo (2 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% in placebo patients (P=.003).
Patients receiving vismodegib experienced grade 1 or grade 2 adverse events that included dysgeusia, loss of weight and hair, and muscle cramps as opposed to patients in the placebo group. This resulted in 54% of the vismodegib group (n=14) discontinuing treatment.
Researchers also determined through basal cell carcinoma biopsies that after 1 month, patients receiving vismodegib decreased hedgehog target-gene expression by 90% (P<.001) in GLI1 messenger RNA. 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.”
Disclosure: See the study for a full list of relevant disclosures.
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