A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma

作者：Sofen Howard^*; Gross Kenneth G; Goldberg Leonard H; Sharata Harry; Hamilton Tiffani K; Egbert Barbara; Lyons Benjamin; Hou Jeannie; Caro Ivor

来源：Journal of the American Academy of Dermatology, 2015, 73(1): 99-U180.

DOI：10.1016/j.jaad.2015.03.013

• basal cell carcinoma
• hedgehog pathway inhibitor
• vismodegib

Background: Vismodegib is approved for treatment of advanced basal cell carcinoma.
Objective: We sought to characterize vismodegib efficacy and safety in operable basal cell carcinoma.
Methods: Patients with new, operable, nodular basal cell carcinoma received vismodegib (150 mg/d) followed by excision and Mohs micrographic surgery to ensure clear margins. Cohort 1 received vismodegib for 12 weeks; cohort 2 received vismodegib for 12 weeks, then 24 weeks of observation before excision; and cohort 3 received vismodegib for 8 weeks on/4 weeks off/8 weeks on.
Results: In all, 24 patients enrolled in cohort 1, and 25 in cohorts 2 and 3. Complete histologic clearance was achieved by 42%, 16%, and 44% of patients in cohorts 1, 2, and 3, respectively. Muscle spasms (76%), alopecia (58%), and dysgeusia (50%) were the most frequent adverse events (AEs). Five (7%) patients discontinued treatment because of an AE. AE reversibility was evaluated in cohort 2 with 24 weeks of observation after treatment discontinuation.
Limitations: Nonrandomized, small cohort sizes, and short observation durations for some patients are limitations.
Conclusion: Primary efficacy end points were not met (predefined complete histologic clearance rate: >50% in cohorts 1 and 3; >30% in cohort 2). Safety was comparable when dosed continuously versus intermittently. Posttreatment reversibility of vismodegib- related AEs was demonstrated.

• 出版日期2015-7