In patients with basal-cell nevus syndrome, treatment with the hedgehog pathway inhibitor, vismodegib, reduced basal-cell carcinoma tumor burden, though adverse events frequently led to treatment interruption, according to a study published in The Lancet Oncology.1
Hedgehog pathway signaling plays a key role in the development of basal-cell carcinoma. Researchers therefore evaluated the efficacy and safety of vismodegib in patients with basal-cell nevus syndrome.
For the multicenter, double-blind, phase 2 trial (ClinicalTrials.gov Identifier: NCT00957229), researchers enrolled patients aged 35 to 75 years with basal-cell nevus syndrome and at least 10 basal-cell carcinomas eligible for resection. Participants were randomly assigned 2:1 to receive vismodegib or placebo. A total of 37 patients were subsequently enrolled in an open-label phase to continue vismodegib for up to 36 months.
After a median follow-up of 36 months, results showed that the 26 patients treated with vismodegib had an average reduced rate of new surgically eligible basal-cell carcinomas compared with those given placebo. Patients who received vismodegib had an average of 2 new surgically eligible basal-cell carcinomas per patient per year, vs 34 new carcinomas per patient that received placebo per year.
Only 17% of patients tolerated vismodegib continuously for the full 36 months of treatment. Patients who interrupted treatment had an average of 1.7 new surgically eligible basal-cell carcinomas per patient per year, vs 0.6 for those who received treatment continuously.
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Six patients treated with vismodegib reported weight loss of 20% or more; 2 patients had grade 3 to 4 muscle cramps.
Though vismodegib appeared to be efficacious in this setting, further studies are warranted to reduce toxicity associated with vismodegib.
- Tang JY, Ally MS, Chanana AM, et al. Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Nov 9. doi: 10.1016/S1470-2045(16)30566-6 [Epub ahead of print]