New skin cancer drug cited as therapeutic breakthrough

by Bruce Sylvester taken from the New England Journal of Medicine (NEJM)

Vismodegib (Erivedge), a new skin cancer drug for advanced basal cell carcinoma, was called “the greatest advance in therapy yet seen” for advanced basal cell carcinoma in an editorial on June 12  in the New England Journal of Medicine.

“It is a landmark day for patients with basal cell carcinoma and all those involved in their care,” said the NEJM editorial. The editors noted that additional study of Hedgehog pathway inhibitors like vismodegib now warranted.

Most instances of basal cell cancer can be effectively treated, but in some cases, the cancer cells spread and develop an aggressive form of the cancer that does not respond to standard surgical treatment.

“For a small percentage of patients, basal cell carcinoma can progress to inoperable life-threatening, locally advanced or metastatic tumors. Vismodegib, taken as a once a day pill, represents an opportunity to improve quality of life for these patients,” said Dr. Glen Weiss, Director of Thoracic Oncology at Virginia G. Piper Cancer Center Clinical Trials and Clinical Associate Professor of TGen’s (Translational Genomics Research Institute in Phoenix, Arizona) Cancer and Cell Biology Division.

The drug received FDA approval on Jan. 30, 2012, to treat inoperable basal cell carcinoma, the first drug approved for this condition.

Early trial results led to additional study sponsored by Genentech, and approval within 5 years. FDA approval in five years is a notable event since clinical trials typically progress through three phases and can take up to 15 years.

The successful Phase I study at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale (Arizona) Healthcare led to a broader study.

“The first patient put on this drug had advanced basal cell cancer, so we suspected that the tumor had the mutation this drug is targeted against,” said Ramesh K. Ramanathan, M.D., Medical Director at Virginia G. Piper Cancer Center Clinical Trials and Clinical Professor and Deputy Director of the Clinical Translational Research Division at TGen

The follow-up study, a Phase 2 clinical trial of basal cell carcinoma (BCC), was headed by Dr. Aleksandar Sekulic, Assistant Professor of Dermatology for the Mayo Clinic in Arizona, and an Assistant Professor in TGen’s Integrated Cancer Genomics Division.

This Phase 2 study provided the efficacy data for vismodegib that led to its approval by the FDA.

“As a result of a strong collaboration between the Valley [Phoenix/Scotttsdale] institutions, clinical development of this new medication, from the first clinical trial to the FDA approval, was led by the Valley researchers,” said Dr. Sekulic, M.D and Ph.D., whose study found that vismodegib shrank advanced basal cell carcinoma tumors in 43 percent of patients with locally advanced disease and in 30 percent of patients whose disease spread to other organs.

The drug blocks the Hedgehog signaling pathway and was approved for treatment of locally advanced and metastatic basal cell carcinomas. Additional research noted encouraging results for patients with inherited genetic susceptibility for development of large numbers of BCC tumors, known as basal cell nevus syndrome.

“The availability of vismodegib and similar medications will really change the way we treat the patients with advanced forms of BCC, who had very limited options to date. In addition, this drug will likely offer a life-changing treatment for patients with basal cell nevus syndrome. It is possible that the drug may also be of benefit in treatment of earlier stages of BCC, and this is currently being evaluated in several clinical trials,” Dr. Sekulic said.