NEW YORK — The hedgehog inhibitor vismodegib demonstrated encouraging activity in patients with basal cell carcinoma, according to results of a single-center study presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
Vismodegib (Erivedge, Genentech) binds to and inhibits smoothened homologue, a transmembrane protein involved in hedgehog signal transduction, according to background information in the study.
Rogerio I. Neves, MD, PhD, FACS, and colleagues from the departments of plastic surgery, dermatology and medical oncology at Penn State Hershey Cancer Institute in Hershey, Pa., evaluated results of patients with locally advanced basal cell carcinoma (LABCC) or metastatic basal cell carcinoma (MBCC) treated with vismodegib between April 2012 and December 2013.
The analysis included 20 patients who were not eligible for surgery or radiation therapy.
All patients received vismodegib 150 mg daily until disease progression, unacceptable toxicity or patient request for discontinuation. The study protocol allowed participants to discontinue treatment for 4 weeks to recover from treatment-related side effects.
Researchers used RECIST criteria to assess objective response. They defined response as a 30% or greater decrease in externally visible or radiographic dimension, or complete resolution of ulceration if visible at baseline. They defined progressive disease as a 20% or greater increase in externally visible or radiographic dimension, new ulceration or a new lesion.
When evaluating patients with multiple lesions, researchers used the sum of the longest diameters to evaluate response and progression.
At the data cutoff point, results showed 13 patients (65%) achieved complete response and seven patients (35%) demonstrated partial response. None of the 13 patients who achieved complete response experienced disease progression at the time of data cutoff.
All patients with LABCC experienced tumor shrinkage, and researchers reported visible reductions in tumor size and improvements in appearance in a majority of patients.
One patient had MBCC to the axillary lymph nodes. After 2 months of treatment, that patient demonstrated clinical objective response based on assessment of pain cessation, weeping and shrinkage of axillary wound. Within 6 months of treatment, the patient achieved partial pathologic response.
All seven patients who achieved partial response underwent surgery. Researchers observed no residual tumor in two of those patients, and they identified minimal residual tumor in five of those patients.
The most common treatment-related side effects were loss of taste (100%), cramps (80%), hair loss (50%), weight loss (30%) and fatigue (10%). One patient asked to discontinue treatment due to loss of taste and cramps.
Large cohort studies are necessary to confirm the long-term efficacy and safety of vismodegib in this patient population, Neves and colleagues concluded.
For more information:
Neves RI. Therapy with hedgehog inhibitors for locally advanced or metastatic basal cell carcinoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 11-12, 2014; New York.
Disclosure: The researchers report no relevant financial disclosures.