MIAMI BEACH – Vismodegib treatment for 3 months prior to Mohs surgery for operable basal cell carcinomas shrunk tumors by 46% and reduced the Mohs defect size by 38%, based on data from an open-label intervention trial. The findings were reported at the annual meeting of the American Academy of Dermatology.
The estimated Mohs surgical defect area (based on tumor size) in the first five patients treated in the single-arm study decreased by a mean of 1.4 cm2 from baseline, and actual Mohs surgical defect size decreased by 1.1 cm2 after a mean of 3.4 months of treatment with vismodegib. The changes were statistically significant.
The Mohs defect size was considered a secondary endpoint, because actual defect size can be influenced by skin tension and lesion location, said Dr. Mina Ally, a research fellow at Stanford (Calif.) University.
Patients included in the study were five adults with a total of seven basal cell carcinomas (BCCs) of varying histologic subtypes. One occurred on the shoulder, and the rest occurred on the face; one was a recurrence. All patients were treated for at least 3 months at a vismodegib dosage of 150 mg daily, and all required only a single Mohs stage of excision.
Vismodegib, an oral hedgehog pathway inhibitor approved for the indefinite treatment of advanced and metastatic basal cell carcinomas (that result from aberrant hedgehog pathway signaling), was generally safe, said Dr. Ally.
"All patients experienced mild grade 1 side effects, including muscle cramps, hair loss, and taste loss, and we only needed to discontinue the medication early – after 2 months – in one patient due to a grade 2 elevation in liver enzymes," she said, noting that all of the adverse events resolved after treatment discontinuation.
Further sectioning of Mohs specimens revealed no evidence of residual BCC in three cases and residual BCC in one case. The diagnosis was equivocal in the remaining cases.
"This was because we were seeing an increased number of aberrant follicular structures after (vismodegib) treatment, which were sometimes difficult to differentiate from residual BCC," Dr. Ally explained.
Further staining using a panel that included pleckstrin homology-like domain, family A, member 1, a hair follicle stem cell marker, helped differentiate the follicular structures from BCC, she noted.
None of the patients experienced tumor recurrence during a median 5 months of follow-up.
The findings are of interest because about 1 million people in the United States are affected by BCCs each year, said Dr. Ally. While vismodegib appears to represent a useful adjuvant therapy when given for 3 months prior to Mohs surgery in some cases, certain challenges must be overcome, she said.
"Suppression of the Hedgehog pathway does appear to alter normal follicular development, and this was causing us difficulty in analyzing our histology specimens," Dr. Ally noted. "Future challenges really lie in interpreting these histology specimens and being able to differentiate these follicular structures from residual BCC, which can confound tumor margin clearance."
Dr. Ally reported having no disclosures.