RALEIGH, N.C. – Vismodegib, the Hedgehog pathway inhibitor approved earlier this year for the treatment of advanced basal cell carcinomas, is now being studied for the treatment of newly diagnosed, operable, nodular BCCs.
In the just-completed first part of an ongoing three-part phase II study, 23 of 24 patients (96%) showed a clinical response to 12 weeks of treatment with vismodegib (Erivedge) at the approved dosage of 150 mg once daily, Dr. Ivor Caro reported at the annual meeting of the Society for Investigative Dermatology.
Ten patients (42%) demonstrated complete histologic clearance at 12 weeks as assessed through independent review by two dermatopathologists after Mohs surgery, noted Dr. Caro, a dermatologist employed by Genentech in San Francisco.
Of note, complete histologic clearance didn’t correlate with the investigator-assessed clinical response at the 12-week time point. That is, of the 10 patients with complete histologic clearance of their tumor, only 5 were rated by clinicians as having a complete response. Another four were characterized by clinicians as having a partial response, and one was scored as having stable disease.
Adverse events were common, and rates were consistent with those seen in other studies of vismodegib. Muscle spasms occurred in 19 of 24 patients, dysgeusia or ageusia in 19, alopecia in 9, fatigue in 5, and nausea in 5 patients. Seven patients collectively experienced nine grade 3 adverse events, mostly muscle spasms.
The second part of the ongoing phase II study is aimed at evaluating the durability of vismodegib-induced complete histologic clearances. Twenty-five patients with newly diagnosed operable nodular BCCs are undergoing 12 weeks of once-daily therapy, followed by 24 weeks of observation, then excision for pathologic review and Mohs surgery for margin assessment.
The third part of the study, just now underway, will evaluate a dosing regimen designed to boost treatment efficacy through longer drug exposure while also improving tolerability. Twenty-five patients will receive once-daily vismodegib for 8 weeks, then 4 weeks off, followed by another 8 weeks of vismodegib, then excision and Mohs surgery.
"This approach is based upon the observation that when the drug is discontinued, adverse events recover very rapidly," Dr. Caro explained.
Roughly 80% of the 2.1 million nonmelanoma skin cancers diagnosed annually in the United States are BCCs, and about 60% of them are nodular BCCs. More than 90% of all BCCs have abnormalities in the Hedgehog signaling pathway that promote carcinogenesis and are hence potentially susceptible to vismodegib.
Dr. Caro is an employee of Genentech, sponsor of the phase II study.