Vismodegib study confirms safety, efficacy for BCC
Armamentarium grows for advanced BCC
The largest vismodegib trial to date reinforces the drug's safety and efficacy in locally advanced and metastatic basal cell carcinoma (LABCC, MBCC), according to a poster presented at the 2016 American Society of Clinical Oncology Meeting. For many patients worldwide, however, the treatment's affordability remains in question.
In the Study of Vismodegib in Patients with Locally Advanced or Metastatic Basal Cell Carcinoma (STEVIE study; NCT01367665), vismodegib 150 mg QD provided benefit for more than 90% of patients, including 68% who responded to treatment and 26.6% who had stable disease after treatment,1 says study co-author Axel Hauschild, M.D. He is professor of dermatology at the University of Kiel in Kiel, Germany.
The massive number of patients treated—1,215—confirms findings of the drug's phase 1 and 3 trials, which included 30 and 100 patients, respectively, he says.
Dallas-based dermatologist and dermatopathologist Clay J. Cockerell, M.D., who performed a small study (unpublished) of vismodegib plus Mohs surgery in large BCCs, says, "The STEVIE paper's findings are very similar to those we saw in our pilot study—vismodegib appears to work. It's a major addition to our therapeutic armamentarium."
Dr. Hauschild says, "The most important finding is the complete response rate of 33% in LABCC in a real-world setting, including multiple institutions in multiple countries." Nearly all new drugs approved for metastatic melanoma and BCC undergo early studies in highly selected patient populations—those with no comorbidities or other underlying malignancies, he explained. "That's not the patient we are typically seeing with advanced BCC."
As a post-approval study, the STEVIE study could include a broad variety of patients, says Dr. Hauschild. The fact that only four patients with MBCC (or 4.8% of the 84 patients with this disease) achieved complete response suggests that "We are most likely curing patients with LABCC, but not with MBCC. Here, the issue is prolonging life." Median progression-free survival in MBCC was 13.1 months, versus 23.2 months for LABCC.
Anthony M. Rossi, M.D., finds it encouraging to have one-year follow-up data from 1,215 patients showing that vismodegib's side effects were mostly low-grade, and expected. He is an assistant attending physician in dermatologic, Mohs and laser surgery at Memorial Sloan-Kettering Cancer Center and an assistant professor of dermatology at Weil Cornell Medical College.
Adverse events (AEs) that impacted more than 50% of study patients included muscle spasms, alopecia and dysgeusia. Such symptoms impact quality of life, says Dr. Hauschild. "But a large BCC, most of which occur on the face or head, also affects quality of life. If you have a benefit, you will certainly tolerate these toxicities." Furthermore, he says, study data reflect that AE frequency and severity decline over time. "If patients can make it through the first three months, they very likely can make it through long-term use."
Dr. Rossi counters that not all patients' side effects diminish. Strategies being explored to reduce side effects include drug holidays and pulsed treatment regimens, says Dr. Cockerell. In the study, average treatment interruption was 22 days.
Although serious AEs were rare, Dr. Rossi adds, dermatologists should be aware that seven treatment-related deaths occurred in the study (though these patients had confounding factors). Additionally, the fact that 40% of patients lost weight, and 25% experienced diminished appetite, indicates that dermatologists should monitor the nutritional status of patients on vismodegib, he says.