• Skin Cancer
• Soft Tissue Cancers
• Dermatology Clinical Trials

• Skin Cancer
• Soft Tissue Cancers
• Dermatology
• Dermatology Clinical Trials

Vismodegib is the first oral hedgehog pathway inhibitor approved by the European Medicines Agency for the treatment of adults with symptomatic metastatic basal cell carcinoma (mBCC) or locally advanced basal cell carcinoma (laBCC), both of which are not suitable for treatment with surgery or radiotherapy. The pivotal Erivance BCC trial [NCT00833417] was an international 2-cohort nonrandomized study of oral vismodegib (150 mg daily) in patients with laBCC or mBCC. The primary analysis (November 26, 2010, data cutoff) found an objective response rate of 30.3% in patients with mBCC (n = 33) and 42.9% in patients with laBCC (n = 63) according to independent review [Sekulic A et al. N Engl J Med. 2012]. The median duration of response (DOR) according to independent review was 7.6 months for both groups.

Aleksander Sekulic, MD, Mayo Clinic, Scottsdale, Arizona, USA, presented the safety and investigator-assessed efficacy results of the analysis, performed 30 months after the primary analysis (May 30, 2013, data cutoff). Ninety-six patients with radiographically measurable laBCC (n = 63) or mBCC (n = 33) were treated with vismodegib until disease progression or intolerable toxicity occurred. The secondary end points included investigator-assessed objective response rate, progression-free survival, DOR, overall survival, and safety.

At the 30-month analysis, the objective response rates were 48.5% in the mBCC group and 60.3% in the laBCC group, which were comparable to the primary analysis results. The median DOR was 14.8 months in the mBCC group and 26.2 months in the laBCC group. The median progression-free survival at the 30-month analysis was 9.3 months in the mBCC group and 12.9 months in the laBCC group. The median overall survival at the 30-month analysis was 33.4 months in the mBCC group but not evaluable in the laBCC group.

The adverse event (AE) profile of vismodegib was consistent with that previously reported. At the 30-month analysis, 58 patients (55.8%) reported grade 3 to 5 AEs. The most common of these were weight loss, muscle spasms, and fatigue. Two of 6 women of childbearing potential (33%) in the laBCC cohort reported amenorrhea. Serious AEs were reported in 36 patients (34.6%), including pneumonia, syncope, hip fracture, heart failure, cellulitis, gastrointestinal hemorrhage, squamous cell carcinoma, pulmonary embolism, deep vein thrombosis, and death.

At the 30-month analysis, 33 all-cause deaths (31.7%) had been reported, compared with 16 (15.4%) at the primary analysis. The most common causes of death were progressive disease (n = 17; 16.3%) and AEs (n = 8; 7.7%). The AEs resulting in death included unknown (n = 3), hypovolemic shock (n = 1), myocardial infarction (n = 1), meningeal disease (n = 1), ischemic stroke (n = 1), and general physical health deterioration (n = 1). None of the deaths were considered by the investigators to be related to vismodegib treatment.

The estimated median DOR substantially improved with vismodegib treatment. The median DOR approximately tripled in the laBCC cohort as compared with the primary analysis result. The safety profile of vismodegib was consistent with that reported in the primary analysis.

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