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


CONCLUSIONS
Nonrandomized, small cohort sizes, and short observation durations for some patients are limitations.


CONCLUSIONS
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.
Department of Medicine/Dermatology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California. Electronic address: hsofen@ucla.edu.
Howard
H
Sofen
Skin Surgery Medical Group Inc, San Diego, California.
Kenneth G
KG
Gross
DermSurgery Associates, Houston, Texas.
Leonard H
LH
Goldberg
Madison Skin and Research Inc, Madison, Wisconsin.
Harry
H
Sharata
Atlanta Dermatology, Vein and Research Center LLC, Atlanta, Georgia.
Tiffani K
TK
Hamilton
Stanford University Medical School, Stanford, California; Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Barbara
B
Egbert
Genentech Inc, South San Francisco, California.
Benjamin
B
Lyons
Genentech Inc, South San Francisco, California.
Jeannie
J
Hou
Genentech Inc, South San Francisco, California.
Ivor
I
Caro
D000328:Adult; D000368:Aged; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome
D000813:Anilides; C538724:HhAntag691; D011725:Pyridines
basal cell carcinoma; hedgehog pathway inhibitor; vismodegib