(UroToday.com) On the second day of the 2021 ANZUP Annual Scientific Meeting, one of the key sessions focused on what is happening for ANZUP trials. Dr. Lisa Horvath and Dr. Jarad Martin presented on trials in prostate cancer.
Dr. Martin began by highlighting work in the more localized end of the spectrum of prostate cancer, emphasizing trials that have readout or are in follow-up including PainFree TRUS-B, ProPSMA, ENZARAD, and RAVES. Many of these trials have contributed to the standard of care and contributed to guidelines. Dr. Martin emphasized that, based on data from RAVES, he sees adjuvant radiotherapy following prostatectomy as being “defunct” with early salvage as the standard of care. The ENZARAD trial of enzalutamide in addition to radiotherapy and androgen deprivation is, in his words, “a victim of its own success” as the efficacy of this approach is meaning that outcomes are taking a long time to accrue.
Moving on to actively accruing trials, Dr. Martin began by discussing the DASL-HICAP trial of darolutamide in both primary treatment and early salvage. In both contexts, this trial includes a randomized comparison of darolutamide or placebo with radiotherapy and ADT. This offers the opportunity to escalate systemic therapy for patients with high-risk features who are at risk of systemic relapse.
The NINJA trial, a collaboration with TROG, will examine a variety of stereotactic radiotherapy regimes in primary prostate cancer treatment.
Dr. Martin then noted a number of trials that are currently in the start-up phase. Again, these range the spectrum from the initial diagnosis to salvage therapy for patients with localized disease. In patients with favorable risk, the DIPPER trial will look at treatment de-escalation with sparing of salvage therapy among men with favorable imaging and PSA kinetics. The CHyPPR trial will examine whether salvage radiotherapy can be temporally compressed, using a registry randomized format. PRIMARY2 looks at the integration of PSMA-PET/CT with MRI in the initial diagnostic setting.
In the context of oligometastatic prostate cancer, Dr. Martin emphasized the importance of trials in this space before treatment becomes an insidious standard of care.
At this point, Dr. Horvath described trials from ANZUP in the metastatic prostate cancer setting. First highlighting completed trials, Dr. Horvath emphasized the success and practice-changing results of both ENZAMET (examining enzalutamide in metastatic hormone-sensitive prostate cancer) and TheraP at the other extreme (examining Lu-PSMA-617 in third-line therapy for metastatic castration-resistant prostate cancer).
These trials are moving towards translational sub-studies which may inform more personalized care. The ENZAMET central biorepository will help to inform the intensification of care.
Dr. Horvath emphasized that, based on data from ENZAMET, there are a subset of men with early progression (in the first 6-12 months) who die in the first 18 months after diagnosis of metastatic disease. Further, there is a subset of men who do well with ADT alone, even out past 5-years following diagnosis.
Thus, better defining the role of systemic therapy intensification is critical. There are numerous clinical factors which may predict outcomes (including number of metastases, visceral disease, de novo metastases, etc). However, other characteristics including PSMA-PET/CT driven stage migration, co-morbidity, and life expectancy are important to direct these decisions. However, in parallel to these clinical characteristics, Dr. Horvath emphasized the importance of understanding disease biology. In this context, the ENZAMET repository allows the assessment of ctDNA, tissue DNA/RNA, germline DNA/SNPs, lipid metabolism, and immune phenotypes. Together, it is hoped that precise treatment options may be able to be driven by these characteristics.
Currently recruiting studies in the advanced prostate cancer space at ANZUP revolve around better delineating the role of lutetium-PSMA in this disease space. The UpFrontPSMA trial will examine this in the metastatic hormone sensitive prostate cancer space while ENZA-P looks at it in the first line metastatic castration resistant prostate cancer space. As there are accepted standards of care in each of these disease spaces, the comparison of Lu-PSMA will be on top of an intensified backbone. In UpFrontPSMA, patients with receive ADT and docetaxel and then be randomized to Lu-PSMA or placebo. In ENZA-P, patients with high-risk castration resistant disease will receive enzalutamide and ADT and then be randomized to potentially receive Lu-PSMA.
Dr. Horvath then highlighted a number of trials which are just starting up. The GUIDE trial is examining a circulating biomarker to guide docetaxel chemotherapy in patients with metastatic castration resistant prostate cancer. This may potentially allow for intermittent docetaxel therapy. The ENZAdapt trial, which has just received grant funding, is examining the role of adaptive intermittent enzalutamide therapy. And finally, the EVOLUTION trial which examines the role of lutetium in combination with checkpoint inhibitors in men with metastatic castration-resistant prostate cancer.
Taken together, Dr. Horvath emphasized that more work both in the mHSPC and in the later lines of therapy for mCRPC is likely warranted. Further, these trials focus on systemic therapeutics and she emphasized the importance of supportive care in these patients.
Presented by: Lisa Horvath, MBBS, Ph.D., Director of the Department of Medical Oncology at Chris O’Brien Lifehouse and Jarad Martin, MD, Associate Professor, Radiation Oncologist, The University of Newcastle
Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Annual Scientific Meeting (ASM), Sunday, Oct 17 – Monday, Oct 18, 2021.