ISTANBUL – Vismodegib-treated patients with locally advanced basal cell carcinoma showed triple the median response duration after 24 months’ follow-up beyond the primary analysis of the drug, Dr. Luc Dirix reported at the annual congress of the European Academy of Dermatology and Venereology.
Vismodegib, the first-in-class oral medication for treatment of advanced BCC, showed a greatly improved duration of response and no new safety signals in updated results from the ERIVANCE BCC trial, which earlier had earned the drug marketing approval from the Food and Drug Administration and European Medicines Agency.
After 24 months beyond what was included in the primary analysis of ERIVANCE BCC (N. Engl. J. Med. 2012;366:2171-9), the median duration of response by investigator assessment in patients with locally advanced BCC increased from 7.6 to 26.2 months, and increased from 7.6 to 12.9 months in those with metastatic BCC.
"The main new fact is that the median duration of response has increased importantly. That’s a very impressive improvement in disease control, especially in patients with locally advanced disease. It’s a major change from what you’ll find in the New England Journal of Medicine publication," observed Dr. Dirix of Sint-AugustinusHospital, Antwerp, Belgium.
Dr. Dirix reported that, with the additional 24 months of follow-up in the ERIVANCE BCC study, median progression-free survival now stands at 9.3 months in the group with metastatic BCC and 12.9 months in those with locally advanced disease. The objective response rate, which was 43% in patients with locally advanced BCC and 30% in those with metastatic disease in the primary analysis, hasn’t changed significantly with the additional follow-up, he said.
The median overall survival was 33 months. Twelve of the original 33 patients in the cohort with metastatic BCC have died of progressive disease, as have 4 of 63 with locally advanced BCC.
The ERIVANCE BCC trial is an open-label, phase II study in which participants were placed on vismodegib at 150 mg once daily until the occurrence of disease progression, intolerable toxicity, or patient request to withdraw. At the latest follow-up, only 13% of the original study population remained on the drug, Dr. Dirix said. Half of the patients with metastatic BCC who discontinued the drug did so because of disease progression, but only 16% of those with locally advanced BCC stopped treatment. Instead, side effects were the main reason locally advanced BCC patients discontinued therapy.
"The additional 24 months of follow-up didn’t result in any new safety signal, but there are numerous side effects, especially muscle spasms, alopecia, dysgeusia, and others, mostly mild or moderate," said Dr. Dirix.
An estimated 1.6 million new cases of BCC were diagnosed in the United States in 2006, making it the most common form of cancer in the country. Most BCCs are readily treated. However, some cases can progress to locally advanced or metastatic BCC, a disfiguring and potentially life-threatening condition that is not treatable surgically or via radiation therapy, and for which no effective therapy existed before. Vismodegib (Erivedge) provides an oral drug option that works as an inhibitor of the hedgehog pathway, which plays a key role in the pathogenesis of most BCCs.
Dr. Ranier Kunstfeld
With vismodegib intended as lifelong treatment in patients with advanced BCC, and considerable research interest in exploring the drug in other forms of BCC, reliable safety data are needed. Also at the EADV Congress, Dr. Rainer Kunstfeld presented new safety information in an interim analysis from an ongoing study known as STEVIE (Safety Events in Vismodegib), the largest study of the hedgehog pathway inhibitor. His report included the first 300 of a planned 1,200 patients with advanced BCC to be placed on vismodegib.
The data underscore the point that advanced BCC is primarily a disease of the elderly. The mean age of the 278 patients with locally advanced BCC is 70 years, and 65 years in the 22 with metastatic BCC. The median treatment duration as of the data cutoff for this analysis was 5.8 months.
Forty-five percent of patients in the locally advanced BCC group have discontinued treatment, as have 32% of those with metastatic disease, Dr. Kunstfeld said. The reasons differed for the two groups. Discontinuation due to disease progression or death was more than twice as common in patients with metastatic BCC. Patients with locally advanced disease were much more likely to halt treatment because of adverse events.
Ninety-three percent of STEVIE participants experienced at least one adverse event. Roughly two-thirds of these side effects were mild or moderate – that is, grade 1 or 2 – while the remainder were grade 3. The incidence of the most common adverse events were muscle spasms in 59% of participants, alopecia in 49%, distorted sense of taste in 41%, loss of the sense of taste in 26%, asthenia in 23%, and weight loss in 16%. These data were consistent with the safety profile seen in the ERIVANCE BCC study, observed Dr. Kunstfeld, a dermatologist at the Medical University of Vienna.