Vismodegib inhibits the Hedgehog signalling pathway by binding to the Smoothened transmembrane protein. This prevents the activation and nuclear localisation of glioma-associated oncogene transcription factors and the induction of Hedgehog target genes, which are involved in abnormal cell proliferation, survival and differentiation in BCC.1
In the pivotal single-arm ERIVANCE BCC trial, patients with metastatic (n=33) or locally advanced (n=63) BCC were treated with oral daily dosing of 150mg vismodegib. Patients received treatment until disease progression, unacceptable toxic effects or discontinuation of the study.1,2
The primary endpoint was objective response rate defined as complete or partial response on two consecutive assessments separated by at least 4 weeks. Locally advanced patients were considered to have responded to treatment if a reduction of at least 30% in tumour size was observed. In the metastatic disease group, response was assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST).1,2
Overall, 30% (95% CI 16-48%) of patients with metastatic disease and 43% (95% CI 31-56%) of those with locally advanced disease responded to treatment, exceeding the hypothesized percentages of 10% and 20%, respectively (p<0.001). The median duration of progression-free survival in both groups was 9.5 months.2
A pregnancy prevention plan is in place for vismodegib owing to its teratogenic risk. Women of childbearing potential must meet the criteria set out in the plan and men and women being treated with vismodegib must use adequate contraception during and after therapy.1
The most commonly reported adverse events were muscle spasm, alopecia, dysgeusia, weight loss and fatigue.1,2
- Erivedge Summary of Product Characteristics, July 2013.
- Sekulic A et al. N Engl J Med 2012; 366: 2171–9.
Further information: Roche