Second Line Salvage Systemic Therapy for Advanced Penile Cancer

In this manuscript, we highlight the importance of understanding the risk factors associated with a high probability for chemotherapy resistance in patients with advanced penile cancer. We highlight the limitations of second-line cytotoxic chemotherapy or radiation, with very poor patients’ survival. Therefore, it is very important for clinicians caring for penile cancer patients to investigate molecular, immune, and human papillomavirus status in patients at risk of relapsed cancer after cisplatin-based chemotherapy. This is important to benefit the patients from immunotherapies with recent approvals based on high tumor mutational burden and to allow for enrollment on clinical trials that use targeted therapy, immune-based therapy, or HPV directed therapy.

This manuscript summarizes the currently available immunotherapy-based trials that are open for accrual for penile cancer patients with relapsed disease, highlighting that most of those studies are using single-agent immune checkpoint blockade in an all-solid tumors population. Other combination trials that are available in basket trials for patients with relapsed advanced penile cancer are nivolumab with ipilimumab, atezolizumab with bevacizumab, atezolizumab with valproic acid, and nivolumab with cabozantinib. We noted that the current clinical trial landscape lacks immunotherapy combinatory trials in the neoadjuvant treatment setting for penile cancer patients. In the era of immunotherapy, investigation of chemotherapy and immune therapy combination in the neoadjuvant setting is justified and should be the interest of future collaborative groups’ clinical trials.

The manuscript also described the recent data from a Phase II clinical showing that dacomitinib, a second-generation pan-HER tyrosine kinase inhibitor, in 28 chemotherapy-naïve patients with locally advanced or metastatic PSCC had clinical benefit with the ORR was 32.1% with median PFS of 4.1 months and OS of 13.7 months. The treatment was relatively well tolerated with only 10% grade 3-4 skin rash as the major toxicity.

Lastly, we discuss the potential role for assessing the penile tumor HPV status, beyond the potential prognostic information, patient with HPV positive tumors could benefit from enrollment to HPV directed trials. We summarized the HPV directed trials that are open for accrual for penile cancer patients in the US.

Written by: Jad Chahoud, MD, MPH, Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida & Andrea Necchi, MD, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy

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