(UroToday.com) During the second day of the 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting (ASM), two sessions examined key trials in ANZUP. The second of these focused on trials in bladder, urothelial, and penile cancers as well as renal cell carcinoma. In this session, Dr. Dickson Hayne provided an update on ongoing trials in bladder, urothelial, and penile cancer.
Dr. Hayne began with a focus on penile cancer. He emphasized that this rare cancer makes study difficult and thus there is a relative paucity of data. However, ANZUP has recently contributed to a registry and outcomes study utilizing the Western Australia Cancer Registry between 1992 and 2017. Over this 25 year time period, the authors identified 186 patients with invasive disease. These men spanned the age range from 20-39 years (7%) to 80 years and older (19%). Annual incidence rates were low, with the maximum number of new diagnoses being 15 cases in 2012.
The authors then examined survival outcomes, stratifying by presumptive risk factors. While they noted that patients who lived in remote and rural regions faired more poorly than those in urban or metropolitan centers and that aboriginal patients or Islanders faired more poorly than those who were white, neither grade nor age appeared to be significantly associated with survival.
However, Dr. Hayne emphasized that nearly one-third of patients were lacking grade information and there was potential under-reporting of aboriginal patients.
Dr. Hayne then moved to a discussion of upper tract urothelial carcinoma. In this disease space, there are no active ANZUP research efforts, though there is considerable interest in multi-center surgical outcomes registries and the POUT2 trial, which, in parallel to the POUT trial of adjuvant chemotherapy following nephroureterectomy, seeks to assess the role of the addition of immunotherapy. However, there have proven to be many logistic issues to the opening of this trial.
Finally, Dr. Hayne moved on to discussing bladder cancer, contextualizing this conversation by highlighting that bladder cancer mortality in Australia has worsened over time.
In nonmuscle-invasive bladder cancer (NMIBC), there are a number of ongoing studies and efforts, though none in the Bacillus Calmette Guérin (BCG)-refractory disease space.
The first project in NMIBC which Dr. Hayne highlighted is the BCG + mitomycin (BCGMM) trial. This Phase III RCT of patients with high-risk NMIBC randomized individuals 1:1 to receive either standard induction BCG followed by maintenance or alternating BCG/mitomycin C (the experimental arm) with the same schedule.
This is an ongoing, and actively recruiting trial, with 15 centers currently accruing patients and more set to join. This trial is particularly timely given the BCG shortage. Use of an alternating BCG + mitomycin treatment regime, if outcomes are proven to be equivalent or better than the accepted standard of care of BCG, would reduce BCG utilization on a per-patient basis to one-third (from 27 to 9 doses).
Moving forward in the disease space, Dr. Hayne emphasized the role of the ANZUP Collaborative Multicenter Cystectomy Database. This database is modeled on the BAUS quality metrics and, based on a REDCap platform, data is input in a prospective fashion. This multi-center database has contributors from across the country. While data are early still, Dr. Hayne presented some of his own data, collected utilizing the registry, examining outcomes for 100 patients undergoing radical cystectomy for bladder cancer between 2015 and 2020.
He reported favorable perioperative outcomes compared with previously published series with serious (Clavien-Dindo grade 3 or greater) complications noted in 12% of patients at 30 days and 16% of patients at 90 days following surgery. Notably, there were no mortalities in the 30 or 90 days following surgery and 1-year mortality was 6%.
He then discussed the Exercyst trial assessing a pre-cystectomy exercise intervention. Of a planned 20 patients, 16 have been recruited thus far. While this study is designed to assess the feasibility of this approach, other efficacy based outcomes including hospital length of stay, 90-day complication rates, and quality of life outcomes will be assessed.
In the muscle-invasive bladder cancer (MIBC) context, he highlighted two trials assessing the optimization of the current standard of care approaches in this disease space. The first, PCR-MIB is a multicenter, single-arm, Phase II trial assessing the safety of adding pembrolizumab to chemoradiotherapy in patients with MIBC. To date, 23 of a planned 30 patients have been enrolled. In addition, there are correlative biologic studies embedded in this trial.
The second, SUBDUE-1, is the first report of sub-urothelial injection of durvalumab prior to cystectomy, designed as a dose-finding phase Ib trial. To date, four patients have been recruited of a planned 12. To be eligible, patients could not have received neoadjuvant chemotherapy and must be scheduled for cystectomy. Two weeks prior to cystectomy, patients receive sub-urothelial injections of durvalumab in a dose-escalation protocol with a planned assessment of pathological outcomes.
In advanced bladder cancer, Dr. Hayne highlighted the BL-12 trial while acknowledging that this disease space is dominated by industry-sponsored, rather than cooperative group, trials.
Finally, he discussed so-called “miscellaneous translational” studies with an emphasis on the ZiPUP study, a single-center, open-label, Phase I trial of 89-Zirconium-labelled girentuximab (89Zr-TLX250) PET in patients with urothelial cancer. This agent is a carbonic anhydrase IX ligand, which would be expected to quite specific for bladder cancer. Further, this agent undergoes hepatic, rather than renal, metabolism with no resultant urinary excretion is to be expected which should improve imaging of the urinary tract.
In closing, Dr. Hayne emphasized the importance of the consumer advisory panel to guide ANZUP trials.
Presented by: Dickson Hayne, MBBS, MD, FRCS, FRACS, Professor, Faculty of Health and Medical Sciences, Surgery, The University of Western Australia, Perth, Australia
Written by: Christopher J.D. Wallis, MD, PhD, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD, during the 2020 Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) Mini Annual Scientific Meeting (ASM), November 29 - 30, 2020