Research in context
Evidence before this study
We searched MEDLINE and Embase with the search terms “basal cell carcinoma”, “BCC”, “vismodegib”, “multiple BCC”, and “Gorlin syndrome” for peer-reviewed articles and abstracts published from Jan 1, 2010, to Oct 1, 2016. Most investigations of vismodegib in clinical trials have been in patients with advanced basal-cell carcinoma. The pivotal ERIVANCE BCC phase 2 trial also included patients with multiple basal-cell carcinomas, including some with basal-cell nevus (Gorlin) syndrome, and showed clinical benefit in this population. Another study by Tang and colleagues showed the efficacy of vismodegib versus placebo in managing basal-cell carcinoma in patients with basal-cell nevus syndrome. Nevertheless, chronic low-grade toxic effects make long-term treatment intolerable for most patients. Therefore, there is a high unmet need for long-term efficacious treatments for patients with multiple basal-cell carcinomas and basal-cell nevus syndrome.
Added value of this study
To the best of our knowledge, the MIKIE study includes the largest population of patients with basal-cell nevus syndrome and multiple basal-cell carcinomas so far. We investigated whether an intermittent regimen of vismodegib could balance activity and toxicity so that growth of basal-cell carcinomas would be inhibited, while improving the overall tolerability to limit the number of patients who discontinued treatment. The primary analysis shows that intermittent dosing of vismodegib was efficacious and tolerable in patients with multiple basal-cell carcinomas. Patients showed meaningful clinical benefit in both treatment groups. The safety profiles of the two regimens were similar, and the range of adverse events was consistent with previous clinical experience.
Implications of all the available evidence
Our results suggest that intermittent dosing schedules could be useful for patients with multiple basal-cell carcinomas who need long-term treatment.