TY - JOUR
T1 - A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma
AU - Sofen, Howard
AU - Gross, Kenneth G.
AU - Goldberg, Leonard H.
AU - Sharata, Harry
AU - Hamilton, Tiffani K.
AU - Egbert, Barbara
AU - Lyons, Benjamin
AU - Hou, Jeannie
AU - Caro, Ivor
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - basal cell carcinoma
KW - hedgehog pathway inhibitor
KW - vismodegib
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UR - http://www.scopus.com/inward/citedby.url?scp=84937968152&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2015.03.013
DO - 10.1016/j.jaad.2015.03.013
M3 - Article
C2 - 25913533
AN - SCOPUS:84937968152
VL - 73
SP - 99-105.e1
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
SN - 0190-9622
IS - 1
ER -