(UroToday.com) The Society of Urologic Oncology (SUO) annual winter meeting included a penile cancer session and a presentation by Dr. Juanita Crook discussing updates of the global InPACT trial. Penile cancer is rare and evidence to establish practice standards is limited. There is suggestion of benefit with neoadjuvant chemotherapy, as well as chemo-radiation being effective for squamous cancers in other sites. There are several important questions that InPACT will address for penile cancer management:
- InPACT Neoadjuvant – What is the role of neoadjuvant therapy? Does either chemotherapy or chemoradiation provide superior outcomes?
- InPACT Pelvis – Among patients with prior inguinal lymphadenectomy and adverse features receiving chemoradiation, what is the role of prophylactic pelvic lymph node dissection? Particularly for patients with >=3 positive nodes and extranodal extension and those with bilateral metastases
Inclusion criteria for the InPACT trial included (i) men >= 18 years of age, (ii) biopsy-proven squamous cell carcinoma of the penis, (iii) clinical T any, N1-N3, (iv) measurable disease by RECIST criteria (>= 1.5 cm short-axis diameter), (v) ECOG performance status 0-2, (vi) patients able/willing to be randomized given preoperative parameters, (vii) laboratory evaluation consistent with potential randomization to various treatment arms (ie. adequate hematologic, renal, and liver function), (viii) willing and able to comply with the follow-up schedule, and (ix) written informed consent. Key exclusion criteria included (i) pure verrucous carcinoma, (ii) squamous cell carcinoma of the urethra, (iii) non-squamous penile malignancy, (iv) stage M1 penile carcinoma, (v) prior chemotherapy or chemoradiotherapy outside of the InPACT trial, (vi) concurrent malignancy (other than SCC skin or basal cell carcinoma) that required any treatment in the last 3 years (low-risk prostate cancer on active surveillance was allowed), (vii) sexually active patients who are unwilling to use effective contraception. The InPACT trial design is as follows:
The InPACT trial is taking a Bayesian approach, with no formal hypothesis testing. This approach does allow for estimating the probability of choosing the better of two therapies in the intention to treat analysis. Overall, this methodology has been accepted for rare cancers. The primary endpoint for this trial is survival and secondary endpoints include DSS, DFS, DMFS, LRFS, pT0 rate, toxicity, surgical complications, and feasibility of delivering treatment on schedule. The original target accrual for InPACT was 400 patients across all international sites, including 200 in North and South America. These sites are through ECOG, SWOG, or Alliance NCTN, NCIC in Canada, and sites in Mexico and Columbia. The current status is that the trial is active in the UK (6 sites open), active in the US (16 open, 2 pending), and active in Canada (1 open, 2 pending). Dr. Crook notes that the total number of patients currently enrolled is 65 with a new global accrual target of 200 patients (which will still meet statistical goals).
The goal of site credentialing is to ensure the site’s ability to effectively carry out protocol-mandated treatment in a multidisciplinary fashion. Thus, there is a credentialing process for surgeons, radiologists, radiation oncologists, and pathologists. The surgeon is the point-person for credentialing, needing to acquire letters of participation from the multi-disciplinary specialists. Additionally, five cases of locally advanced/metastatic penile cancer in the prior 2 calendar years by the team must have case summaries submitted for review by the North American Surgical Oversite Committee (NASOC). The specific radiology credentialing is coordinated by IROC-Philadelphia and the American College of Radiology Curriculum Management. An online training program is also completed to credential radiologists at participating centers prior to recruitment. Pathology credentialing includes the site pathologist reviewing and completing the EA8134 Pathology Credentialing slide deck. Radiation oncology credentialing is coordinated by IROC-Houston, including a questionnaire, contouring two benchmark cases and planning one benchmark case, and a dosimetry audit. Ongoing quality assurance includes submission (within 3 weeks of the procedure) of the inguinal lymph node checklist, pelvic lymph node checklist, intraoperative photographs, and pathology/operative reports, with NASOC review every 2 weeks. Ultimately, this rigorous process will also identify sites with interest and capacity for future multi-institutional penile cancer trials.
Patient specimen tissue banking is encouraged and will be housed at the ECOG Central Tissue Repository at the M.D. Anderson Cancer Center. A future goal is to assess the relationship of potential biomarkers with response/outcome, looking at HPV, p16, p53, EGFR, PD1/PD-L1, etc.
Dr. Crook then provided an update on the trial, specifically information from the ECOG-ACRIN Fall report. To date, 65 patients have been accrued, including 52 patients in the USA. From these 52 patients, this includes 45 patients randomized in InPACT Neoadjuvant (85% completing treatment as per protocol, with 12% discontinuing secondary to disease progression) and 7 patients randomized in InPACT Pelvis (100% completed per protocol). Thus far, the median age is 67 years of age (range 49-84) and the majority of grade 3 adverse events have been hematologic or infectious. There have been four patients with grade 4 hematologic adverse events, and no grade 5 toxicities.
Dr. Crook concluded her update of the InPACT trial by noting that the contact people include Drs. Curtis Pettaway and Philippe Spiess in the USA, Drs. Steve Nicholson and Steve Penegar in the UK, and Drs. Juanita Crook and Max Sherry in Canada.
Presented by: Juanita Crook, MD, FRCPC, British Columbia Cancer Agency, Kelowna, British Columbia, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 Society of Urologic Oncology (SUO) Winter Annual Meeting, Orlando, FL, Wed, Dec 1 – Fri, Dec 3, 2021.