Basal cell carcinoma (BCC) is the most common form of skin cancer in Europe, affecting around 100 people per 90,000 in the UK each year. In most cases, BCC is curable and rarely spreads, although metastasis becomes more likely if treatment is delayed.
Vismodegib inhibits signalling via the so-called ‘hedgehog’ cell growth pathway, which is implicated in more than 90% of BCC cases. If approved, vismodegib will benefit cases of advanced disease, where current treatment options have limited efficacy or (in the case of surgery) are likely to cause disfigurement.
The open-label pivotal phase 2 ERIVANCE BCC study evaluated vismodegib in 104 patients with advanced BCC. Participants included 71 patients with locally advanced BCC (laBCC) whose lesions were inappropriate for surgery and for which radiotherapy was unsuccessful or contraindicated, and 33 patients with metastatic BCC (mBCC). Patients received oral vismodegib 150mg daily until disease progression or intolerable toxicity.
The overall rate of response, defined as tumour shrinkage or healing of visible lesions as assessed by independent review, was 43% in the laBCC cohort and 30% in the mBCC cohort. The median duration of progression-free survival was 9.5 months in both groups.
Common side-effects of vismodegib included hair loss, fatigue, nausea, diarrhoea, muscle spasm, anorexia and weight loss. Serious adverse events occurred in a quarter of patients, but only 4% of these were attributed to vismodegib.
Vismodegib is also being investigated for operable forms of BCC, as well as for metastatic colorectal and ovarian cancers.