New therapy for advanced and metastatic basal cell skin cancer

Study data appears in New England Journal of Medicine

A study published today in the New England Journal of Medicine reports a potential new investigational therapy for advanced and metastatic basal cell skin cancer tested at the Virginia G. Piper Cancer Center at Scottsdale Healthcare and other sites appears to demonstrate tumor shrinkage and limited side effects in patients.

"Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma" is authored by lead investigator Daniel D. Von Hoff, MD, a world-renowned expert in developing new drugs for patients with cancer. Dr. Von Hoff is an oncologist and chief scientific officer at the Virginia G. Piper Cancer Center at Scottsdale Healthcare, physician-in-chief at Translational Genomics Research Institute (TGen) and chief scientific officer at US Oncology.

The article appears online at NEJM.org and will be included in the Sept. 17 issue of New England Journal of Medicine.

These findings are significant because there is no proven therapy for advanced basal cell carcinoma (BCC). BCC is the most common cancer in the United States with about one million new cases diagnosed each year. Arizona has one of the highest incidences of skin cancer in the world.

Typically diagnosed with a simple biopsy, the risk of BCC increases for individuals with a family history or prolonged exposure to ultraviolet (UV) rays from the sun. Most patients are cured by surgery, but if left untreated or if spread to other organs, then scarring and disfigurement, and even death may result.

In a Phase I clinical trial conducted in Arizona at the Virginia G. Piper Cancer Center at Scottsdale Healthcare, Dr. Von Hoff and colleagues at Johns Hopkins University and Karmanos Cancer Institute demonstrated that GDC-0449, a Hedgehog Pathway Inhibitor, appears to shrink tumors in locally-advanced and metastatic basal cell carcinoma (BCC) while having limited side effects including a loss of sense of taste, and a small amount of hair loss and weight loss. GDC-0449 was discovered by Genentech and was jointly validated through a series of preclinical studies performed under a collaboration agreement between Genentech and Curis, Inc. (Cambridge, Mass). Genentech is a wholly-owned subsidiary of the Roche Group.

Known as the "Hedgehog" trial, results suggest a durable clinical benefit, defined as tumor shrinkage visible on X-ray or other physical exam or improvement in symptoms without tumor growth - was observed in 18 of 33 patients evaluated.

"Until now, we did not have any treatments that can effectively slow the tumor growth in these patients with advanced skin cancer. Using the right drug for each cancer, or precision oncology as we call it, has great potential against other cancers as well," said Dr. Von Hoff.

Abnormal activation of the Hedgehog signaling pathway appears to be an important mechanism for many different types of cancers to develop, survive or grow. This pathway can be inactivated by a chemical called cyclopamine found in the California corn lily. Initial observation and isolation of cyclopamine from the corn lily was made in 1957. Subsequently, scientists at Genentech developed an oral drug called GDC-0449 which can inhibit key components of the Hedgehog pathway.

Basal cell cancer was chosen as the first cancer to be studied, as most BCCs have abnormalities or mutations of Hedgehog pathway genes named PATCHED and SMOOTHENED.

"Success of this new therapy is another example of applying genetic information to medicine. We are constantly working to improve treatment options for patients with common and rare cancers," said Dr. Glen J. Weiss, part of Dr. Von Hoff's team and contributing author for this study.

Patient response to the therapy was assessed through physical examination and imaging. "Integrating genomic data with state-of-the-art clinical and imaging information to develop and apply targeted therapies has certainly taken a major step forward with the encouraging results from the Hedgehog trial," added Dr. Ron Korn, a Scottsdale Healthcare radiologist and director of Scottsdale Medical Imaging Ltd.

Cancer research at Scottsdale Healthcare is administered through its research arm, the Scottsdale Clinical Research Institute.

Dr. Von Hoff's team sees patients in the TGen Clinical Research Services clinic in the Virginia G. Piper Cancer Center at Scottsdale Healthcare. The cancer center is located on the campus of Scottsdale Healthcare Shea Medical Center.

The trial sponsored by Genentech also included sites at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore and Karmanos Cancer Institute in Detroit.