SUO 2017: InPACT Trial - Answering the Unanswered Questions

Washington, DC (UroToday.com) The International penile advanced cancer trial (InPACT) is likely the most important clinical study undertaken to date in the field of advanced penile cancer. Very little high-level evidence currently exists in this space, mainly because of the rarity of the disease. A broad international collaboration was required that harnessed the energy of cooperative groups in Europe and the U.S. to gather enough patients to make a meaningful study. Dr. Curtis Pettaway, the study chair for U.S. clinical sites, presented an overview of the trial and its intended endpoints.

The background for this trial is the fact that clinically detected N+ disease portends a nearly universally dismal diagnosis. Historically, these patients were often treated with surgery alone; but the use of chemotherapy and chemoradiation are increasingly filling the treatment void. TIP chemotherapy is the standard of care for advanced penile cancer, with the most important agent likely being cisplatin. TIP has a 50% 5yr DSS in responders who are clinically N2-3.

The main questions investigators aim to answer in the InPACT trial include the following. What is the role of neoadjuvant therapy in clinically N+ patients? Does chemotherapy or chemoradiotherapy provide superior outcomes? Among patients who had prior inguinal LND with adverse features, what is the role of prophylactic pelvic LND + chemoXRT vs. chemoXRT-alone.

Eligibility includes any clinically N+ patients with penile SCC. Exclusion criteria include clinical M1 status and those with prior chemotherapy or XRT. Randomization was based on disease burden, which is a unique and clinically important stratification built in to this trial.

Low-risk patients undergo ILND without neoadjuvant therapy.
Intermediate-risk patients are randomized to surgery-alone, neoadjuvant chemotherapy, or neoadjuvant chemoradiotherapy.
Intermediate-risk & high-risk patients with GFR < 50 are randomized to surgery-alone or neoadjuvant chemoradiation.
High-risk patients are randomized to neoadjuvant chemotherapy vs. neoadjuvant chemoradiotherapy.
After surgery, all pathology is assessed and patients with adverse features are subsequently randomized to chemoradiotherapy + prophylactic pelvic LND vs. chemoradiotherapy-alone. This arm of the study aims to determine the value of PLND.

The study was set up using the Bayesian approach, which does not aim to answer specific hypothesis and changes structure as results accrue. Treatments would be accepted if the probability of the hazard ratio <1 is at least 60%. The aim for accrual is 400 patients, internationally, with 20 clinical sites over 5 years. There are extensive procedures for quality assurance with various checklists, photos during surgery, etc..

The outcome of this study will make major impacts in the treatment of advanced penile cancer. It will be the first well-powered Level 1 evidence that assesses the value of neoadjuvant therapy and the role of PLND for clinically N+ patients. Analysis by risk group will help clinicians understand if treatment effects vary by underlying disease aggressiveness. The many study investigators and study leaders should be strongly commended for taking on such a monumental and meaningful study!

Presented by: Curtis Pettaway, MD Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX

Written by: Shreyas Joshi, MD, @ssjoshimd Fox Chase Cancer Center, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC

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