Multicenter phase 2 trial of vismodegib plus radiation therapy for locally advanced, unresectable basal cell carcinoma

Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatifactory. Vismodegib is a hedgehog pathway inhibitor that may radiosensitize BCC. In a multicenter phase 2 trial in the United States, patients with LA BCC received 12 weeks of induction vismodegib followed by 7 weeks of concurrent vismodegib and RT. LRC at one year after end of treatment (primary endpoint) was achieved in 91% (95% CI 68-98) of patients, with a response rate of 63% (38-84) after induction vismodegib and 83% (59-96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, PFS and OS rates at 5 years were 78% and 83%, respectively. There was no distant metastasis or BCC-related death. No grade 4 or 5 treatment-related adverse events occurred. Patient-reported quality of life (PRQOL) demonstrated clinically meaningful improvements in all subscales. The authors conclude that in patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.