Vismodegib Efficacy in Advanced Basal Cell Carcinoma Maintained with 8-Week Dose Interruptions: A Model-Based Evaluation

Long-term use of vismodegib is associated with treatment-emergent adverse drug reactions in clinical trials of patients with locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC). Treatment interruptions have been recommended for management of adverse drug reactions, but there is no clear guidance on the duration of those interruptions. A model-based evaluation was conducted to assess the impact of treatment interruptions on vismodegib efficacy. A tumor growth-inhibition model was developed and model-based simulations were performed to assess the proportion of patients achieving ≥30% reduction from baseline in tumor size (ie, proportion of responders) for various dosing schedules. The most conservative simulated scenario compared an intermittent dosing schedule of 12 weeks of vismodegib treatment followed by 8-week dosing interruption (repeated four times for a total duration of 80 weeks) versus 80 weeks of continuous dosing, which predicted a decrease in responders of -4.7% from 90.7% in laBCC and -3.7% from 63.0% in mBCC. These results demonstrated maintenance of vismodegib efficacy with the intermittent dosing schedule and support the recently approved recommendations of treatment interruptions of up to 8 weeks to manage tolerability in laBCC or mBCC patients in the vismodegib US prescribing information.