SUO 2017: When First Line Chemotherapy Fails - Locally Advanced or Metastatic Penile Cancer Patient
Dr. Sonpavde starts his talk discussing the available prognostic factors associated with survival. In several small and retrospective trials visceral metastases and poor performance status have been associated with poor prognosis. In a study by the speaker (Urol Oncol 2014), assessing the prognostic value of this factors showed that overall survival (OS) was significantly decreased from 17 months to 8 and 5 months in patients presenting with one or both risk factors, respectively. Other agents, like paclitaxel, has been studied in the second line setting with disappointing results. The role of salvage surgery in patients who failed cisplatin therapy was also presented and no added benefit was found. Whole genome sequencing of penile cancer was recently reported, noting very few recurrent copy number alterations. Recurrent mutations were noted in the CSN1 and FAT1 pathways which are related to notch 1 signaling identifying a possible site for targeted therapy. In a recent publication (Eur Urol Focus 2015) expression of MAML2 was shown to be a poor prognostic marker for survival, identifying the first genomic signature associated with prognosis in metastatic penile cancer.
Several new systemic therapies are currently being evaluated which include HPV virus targeted immunotherapy, EGFR anti-bodies and PD-L1 therapy. The HPV virus has been identified in approximately 50% of penile cancer patients, making it an attractive targetable pathway. Currently there are four clinical trial using a combination of T-cell targeted and peptide vaccination against the HPV virus and its E7 pathway which are showing promise. EGFR protein has been found to be over-expressed in metastatic penile cancer patients, prompting the use of EGFR antibodies for the treatment of the disease. Initial case reports had shown promise in patients showing significant over-expression, translation of this therapies to clinical setting have been somewhat disappointing with modest improvements in survival. Lastly, PD-L1 expression in penile cancers has been noted to be high, ranging 30-50%, which is higher than any other GU malignancy. Currently there are four trials recruiting patients which are studying the role of PD-1 inhibitor either alone or in combination with chemotherapy or CTLA4 inhibitors, which hopefully will add some improvement to current survival of these patients.
In summary, current systemic therapy confers dismal outcomes, noting the need for better prognostic biomarkers and therapies. There currently several phase I trials assessing targeted agents or immunotherapies which hopefully will add some survival advantage.
Presented by: Guru Sonpavde, MD Oncology Boston, MA, Genitourinary Oncology, Director, Bladder Cancer, Dana Farber Cancer Institute
Written by: Andres F. Correa, Society of Urologic Oncology Fellow, Fox Chase Cancer Center-Temple Health, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC