New data published today in The Oncologist by Siraj M. Ali, M.D., Ph.D., our very own associate director, clinical development and medical affairs, along with our collaborators, revealed clinically relevant genomic alterations in penile squamous cell carcinoma (PSCC), a rare cancer for which the oncogenic drivers have not been well understood up to this point.

The incidence of penile cancer in the United States in 2015 is estimated to be 1,800 cases, but survival rates vary dramatically based on the stage of the disease. Stage I cases have an estimated 10-year survival of 89%; however, in contrast, PSCC patients with metastatic disease only have an estimated survival of 21% at two years. Despite the poor prognosis of advanced PSCC, NCCN guidelines are based largely on small prospective or retrospective studies rather than randomized trials due to the rarity of this disease.

A challenge in developing new therapeutics options for PSCC has been the limited understanding of the oncogenic drivers of disease, particularly human papillomavirus (HPV) infection. HPV has been associated with 50-70% of cases of PSCC, but these studies have combined early- and late-stage PSCC patients who likely have distinct disease pathology and biology. Broader molecular studies of penile cancer have been performed in a limited number of patients, but again, results are confounded due to the combination of early- and late-stages cases and diagnostic methodologies used.

In this study, Foundation Medicine reported results of comprehensive genomic profiling with FoundationOne in the course of clinical care of 20 patients with advanced PSCC. Seventeen (85%) cases were grade IV and three cases (15%) were grade III. Comprehensive genomic profiling revealed 109 genomic alterations (5.45 per tumor), 44 of which were clinically relevant (2.2 per tumor). At least one clinically relevant genomic alteration was detected in 19 (95%) cases, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. High-risk HPV was present in 10% of patients, which was low relative to other HPV-associated squamous carcinomas, such as cervical cancer.

These data represent an important step forward in exploring new treatment options for patients suffering from this rare and difficult-to-treat cancer. Read the full study here.