Two intermittent vismodegib dosing regimens for long-term treatment demonstrated good activity among patients with multiple basal cell carcinomas, according to a study published in The Lancet Oncology.1
Vismodegib, a first-in-class Hedgehog pathway inhibitor, is approved for the treatment of adults with advanced basal cell carcinoma. Patients with multiple basal cell carcinomas, including those with Gorlin (nevoid basal-cell carcinoma) syndrome, require extended vismodegib treatment. Researchers evaluated the activity and safety of 2 long-term intermittent dosing regimens in this population.
For the double-blind, phase 2 trial (MIKIE; ClinicalTrials.gov Identifier: NCT01815840), investigators enrolled 229 adult patients with multiple basal cell carcinomas, including those with Gorlin syndrome, who had at least 6 clinically evident basal cell carcinomas.
Participants were randomly assigned 1:1 to receive vismodegib 150 mg orally once daily either in an intermittent schedule of 12 weeks of vismodegib followed by 8 weeks of placebo (arm A) or as 24 weeks induction followed by an intermittent schedule of 8 weeks of placebo followed by 8 weeks of vismodegib (arm B). Total treatment time for both arms was 72 weeks.
At week 73, the average number of basal cell carcinoma lesions was 62.7% (95% CI, 53.0-72.3) lower than baseline in arm A and 54.0% (95% CI, 43.6-64.4) reduced from baseline in arm B.
Ninety-five percent of the 227 evaluable patients had at least 1 treatment-emergent adverse event (94% in arm A vs 97% in arm B). The most frequently reported grade 3 or worse treatment-related adverse events were muscle spasms, elevated blood creatine phosphokinase, and hypophosphatemia.
Nineteen percent of patients in arm A and 17% of patients in arm B reported serious treatment-emergent adverse events. One patient in arm A died of a pulmonary embolism, which was potentially related to vismodegib-treatment.
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Arm A appeared to be associated with better activity, fewer toxicities, and improved adherence compared with arm B.
- Dreno B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 2017 Feb 7. doi: 10.1016/S1470-2045(17)30072-4 [Epub ahead of print]