Press Release

Nearly All Advanced Penile Cancers Harbor Drug-Targetable Mutations

DURHAM, N.C., Dec. 14, 2015 /PRNewswire-iReach/ -- New findings show that 95% of advanced penile cancers harbor one or more genomic mutations associated with targeted therapy, according to a study published in The Oncologist on December 14, 2015. These findings suggest that patients may benefit from a range of current and emerging therapies known to target these mutations.

Each year, penile squamous cell carcinoma (PSCC) is diagnosed in 1,800 men in the United States and is responsible for approximately 320 deaths. Although the 10-year survival rate is high (89%) for patients diagnosed with stage I disease, few treatment options are available for advanced PSCC. Platinum-based chemotherapy, the current standard of care for metastatic PSCC, is associated with survival rates of one year or less. New treatment options are urgently needed to prolong survival and improve outcomes for these patients.

Although research is underway to better understand PSCC, most studies to date have focused on the role of human papilloma virus (HPV) on tumor development and progression. Little is known about other potential drivers of PSCC, including the underlying genomic alterations that may be vulnerable to treatment.

To identify new treatment targets, a team of researchers led by Jeffrey Ross, MD, Medical Director of Foundation Medicine, Inc., performed comprehensive genomic profiling of PSCC tumor samples. The goal of the study was to detect clinically relevant genomic alterations (GAs), which are defined as abnormalities linked to approved or investigational targeted therapies.

"Whether in the setting of routine practice or clinical trials, comprehensive genomic profiling offers the possibility of guiding the rational use of targeted therapy for patients with advanced PSCC," Dr. Ross said. As an example, therapies such as cetuximab, which targets the epidermal growth factor receptor (EGFR), may be effective against tumors with underlying mutations in the EGFR gene.

Dr. Ross and colleagues performed comprehensive genomic profiling on 20 tumor specimens harvested from patients with grade IV (n = 17) or grade III (n = 3) penile cancer. The genomic tests focused on mutations or other abnormalities that could be targeted with current or emerging drug therapies.

Comprehensive genomic profiling revealed 109 total genetic alterations, or 5.45 mutations per tumor. In total, 95% of tumors harbored at least one clinically relevant GA, with an average of 2.2 drug-targetable alterations per tumor.

The diverse mutation profiles of the PSCC tumor samples suggested potential vulnerability to a broad range of targeted therapies. The most common clinically relevant GAs included abnormalities affecting CDKN2A (40%), NOTCH1 (25%), PIK3CA (25%), EGFR (20%), CCND1 (20%), BRCA2 (11%), RICTOR (10%), and FBX27 (10%).

Given the high frequency of clinically relevant mutations, potential therapeutic advances for PSCC may be on the horizon. "Of note, 55% of tumors harbored mutations in either EGFR or PIK3CA/FBXW7, suggesting a possible clinical benefit from treatment with cetuximab or mTOR inhibitors, respectively," stated Siraj Ali, MD, PhD, Director, Clinical Development and Medical Affairs at Foundation Medicine. "These findings provide a strong rationale for prospective trials of targeted therapies toward these mutations," he concluded.

Fred R. Hirsch, MD, PhD, Professor of Medicine and Pathology at the University of Colorado Cancer Center and School of Medicine in Denver, and an Editor of The Oncologist, commented, "This work provides a real-world profile of the genomics of penile cancer, shedding light on the molecular underpinnings of this rare disease. These findings will help to identify treatment options where few currently exist and will also be useful in guiding the development of future clinical trials directed at advanced PSCC patients with specific genomic alterations."

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Article: "Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests A High Frequency of Clinically Relevant Genomic Alterations," Ali SJ, Pal SK, Wang K, et al. (DOI: 10.1634/theoncologist.2015-0241). The article can be accessed at The Oncologist.