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Michael Schweizer, MD, of the University of Washington and Fred Hutchinson Cancer Center, discusses findings from a randomized dose-expansion study of the investigational EZH2 inhibitor mevrometostat in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) (Abstract LBA138).
Neeraj Agarwal, MD, FASCO, of Huntsman Cancer Institute, presents data from cohort 1 of the phase III TALAPRO-2 trial—final overall survival data, an update on radiographic progression–free survival, and safety follow-up—which included patients with metastatic castration-resistant prostate cancer (mCRPC) unselected for homologous recombination repair gene alterations (Abstract LBA18).
Karim Fizazi, MD, PhD, of Institut Gustave Roussy, University of Paris-Saclay, reviews final overall survival results from cohort 2 of the phase III TALAPRO-2 trial, which investigated the combination of talazoparib and enzalutamide in patients with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) (Abstract LBA141).
William Aronson, MD, of the VA Greater Los Angeles Healthcare System, discusses findings from the CAPFISH-3 trial, which investigated whether a high omega-3, low omega-6 fatty acid diet with fish oil capsules decreased Ki-67 levels in men with prostate cancer on active surveillance (Abstract 312).
Masood Moghul, PhD, of The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, describes the impact of a nurse-led mobile clinical unit on targeted screening invitations to men at high risk for prostate cancer in disadvantaged communities in London (Abstract 317).
Omid Yazdanpanah, MD, of the University of California, Irvine, presents findings from a secondary analysis of the VISION trial, which compared the efficacy and safety of LuPSMA in patients treated with vs without concomitant androgen receptor pathway inhibitors (ARPIs) (Abstract 121).
Nicholas D. James, PhD, FRCP, MBBS, of The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, discusses findings from an embedded phase II randomized study from the STAMPEDE trial. The study assessed the efficacy and toxicity of transdermal estradiol patches vs luteinizing hormone–releasing hormone analogs in patients with M1 prostate cancer (Abstract 21).
Benjamin Maughan, MD, PharmD, of Huntsman Cancer Institute, discusses the effects of a 12-week, structured, guided exercise program called Personal Optimism With Exercise Recovery (POWER) on fatigue and peak aerobic exercise capacity in patients with advanced prostate cancer receiving androgen-deprivation therapy (Abstract 120).
Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Samuel R. Denmeade, MD, of Johns Hopkins University School of Medicine, discuss a study showing that patients with metastatic castration-resistant prostate whose disease is progressing on abiraterone with androgen-receptor alterations detected in the blood may benefit from bipolar androgen therapy. Routine liquid biopsy testing may enable further adoption of bipolar treatment (Abstract 5003).
Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, PhD, of Institut Gustave Roussy and the University of Paris-Saclay, discuss a second interim analysis of the health-related quality of life and pain outcomes in the PSMAfore study (Abstract 5003).
Christos Kyriakopoulos, MD, of the University of Wisconsin Carbone Cancer Center, discusses data suggesting that adding cabazitaxel to abiraterone and prednisone improves progression-free survival in patients with metastatic castration-resistant prostate cancer who previously received chemohormonal therapy with docetaxel for hormone-sensitive disease compared with abiraterone plus prednisone alone (Abstract LBA5000).
Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Susan Halabi, PhD, of the Duke Cancer Institute and Duke University School of Medicine, discuss a clinical-genetic model that identified novel circulating tumor DNA alterations that are prognostic of overall survival and may help to classify patients with metastatic castration-resistant prostate cancer into risk groups useful for selecting trial participants (Abstract 5007).
Anthony M. Joshua, MBBS, PhD, of Princess Margaret Cancer Centre, discusses results from the MAST study, which explored the question of whether metformin could reduce disease progression in men with low-risk prostate cancer who are undergoing active surveillance (LBA5002).
Sumanta K. Pal, MD, of City of Hope, discusses the ways in which the composition of the gut microbiome may impact the outcome of immune therapy. Methods such as fecal microbiome transplant hold promise as a means of augmenting the effect of treatment and, according to Dr. Pal, potentially resensitizing patients to therapies.
Umang Swami, MD, of Huntsman Cancer Institute at the University of Utah, describes the molecular and immunologic mechanisms of metastatic tropism in advanced prostate cancer, data that may facilitate future drug development. In patients with metastatic disease, specific sites are associated with differential overall survival, but the biological reasons have not been fully explored (Abstract 21).
Maha H.A. Hussain, MD, of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, discusses phase II findings from the BRCAAway trial. This study showed that in patients with metastatic castration-resistant prostate cancer with BRCA1/2 or ATM alterations, abiraterone and prednisone plus olaparib was well tolerated and resulted in a longer progression-free survival than either agent alone or sequentially.
Neeraj Agarwal, MD, of Huntsman Cancer Institute at the University of Utah, discusses results of the CONTACT-2 trial, which showed cabozantinib plus atezolizumab improved radiographic progression–free survival of patients with metastatic castration-resistant prostate cancer vs a second novel hormonal therapy (NHT) in patients who had experienced disease progression on a prior NHT and have extrapelvic nodal or visceral disease. The benefits were more pronounced in patients with liver metastasis and in those who previously received docetaxel (Abstract 18).
Rana R. McKay, MD, of the University of California, San Diego, discusses phase II findings from the Neptune study of neoadjuvant olaparib plus androgen-deprivation therapy followed by radical prostatectomy in patients with intermediate-risk or high-risk prostate cancer marked by germline or somatic BRCA1/2 gene alterations. This population generally has inferior outcomes, and PARP inhibition has shown efficacy in these patients.
Stephen J. Freedland, MD, of Cedars-Sinai Medical Center, discusses the incidence of prostate cancer in transgender women. Although the rates of disease appear lower than in cisgender men, Dr. Freedland notes the risk is not as limited as case reports may suggest. He also discusses interpreting PSA values and rises in PSA for patients on gender-affirming hormone therapies.
Samson W. Fine, MD, of Memorial Sloan Kettering Cancer Center, discusses the evolving spectrum of atypical intraductal proliferations in the prostate, from high-grade prostatic intraepithelial neoplasia to intraductal carcinoma. He describes several clinical challenges, including: assessment and terminology of cribriform architecture; pathologic reporting in various biopsy scenarios; and association with genetic findings.
William J. Catalona, MD, of Northwestern University Feinberg School of Medicine, reviews the genetic landscape in prostate cancer, including BRCA2 and ATM, two important mutations for aggressive disease; the clinical implications of germline testing such as guiding screening and disease management, as well as identifying patients at high risk for aggressive prostate cancer; and the role of somatic testing, especially in advanced disease.
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).
Alicia K. Morgans, MD, MPH, and Praful Ravi, MRCP, MBBChir, both of Dana-Farber Cancer Institute, discuss an individual patient-data analysis of randomized trials from the ICECAP collaborative. A PSA nadir of ≥ 0.1 ng/mL within 6 months after radiotherapy completion was prognostic for prostate cancer–specific, metastasis-free, and overall survival in patients receiving radiotherapy plus androgen-deprivation therapy for localized prostate cancer. These findings may help identify patients for therapy de-escalation trials (Abstract 5002).
Alberto Bossi, MD, of Institut Gustave Roussy, discusses phase III findings showing that combining prostate radiotherapy with systemic treatment did not improve overall survival in men with de novo metastatic castration-sensitive prostate cancer and low metastatic burden. However, best outcomes (radiographic progression–free-survival and overall survival) were observed in men receiving the standard of care plus abiraterone acetate plus prednisone with radiotherapy (Abstract LBA5000).
This is Part 3 of Novel Hormonal Therapies for Prostate Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Alicia K. Morgans, Neeraj Agarwal, and David VanderWeele discuss the management of locally advanced high-risk prostate cancer. The patient is a 57-year-old man who presents to his urology with increasing nocturia symptoms. His PSA is 12.4 ng/mL, and an MRI shows a PI-RADS 5 lesion in the right apex concerning for prostate cancer. Biopsy confirms Gleason 4+4 prostate adenocarcinoma, and several retroperitoneal lymph node metastases are revealed on PSMA PET scan. He is found to have a germline BRCA2 mutation, and his team is considering treatment with radiation plus androgen-deprivation therapy, abiraterone acetate, and prednisone per STAMPEDE. The faculty discuss the optimal treatment workup for patients with locally advanced high-risk prostate cancer, the importance of germline genetic testing, the benefits of intensified treatment with ADT plus abiraterone acetate, and the role of gonadotropin-releasing hormone antagonists in improving testosterone recovery and maintaining quality of life.
This is Part 2 of Novel Hormonal Therapies for Prostate Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Alicia K. Morgans, Neeraj Agarwal, and David VanderWeele discuss the management of de novo metastatic hormone-sensitive prostate cancer. The patient is a 74-year-old man who presents to his primary care physician due to worsening back pain. An x-ray reveals an area in T12 concerning for metastatic cancer, and his PSA is found to be 23 ng/mL. He completes staging workup, which demonstrates multifocal bone metastases and metastatic disease in the liver, and he is started on androgen-deprivation therapy (ADT) as initial treatment for his metastatic disease. The faculty discuss ways to reduce the risk of complications from ADT for patients with metastatic hormone-sensitive prostate cancer, the role of intensified treatment with couplet or triplet ADT combinations, and the importance of co-management with primary care or cardiology.
This is Part 1 of Novel Hormonal Therapies for Prostate Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Alicia K. Morgans, Neeraj Agarwal, and David VanderWeele discuss biochemical recurrence in prostate cancer. The patient is a 64-year-old man with a history of localized prostate cancer treated with radical prostatectomy, Gleason 4+4, and positive extracapsular extension and positive right apical margin. Due to high-risk features, he underwent adjuvant radiation therapy. Although his PSA was initially undetectable, it started to increase after 2 years, reaching 12.9 ng/mL. He was negative for evidence of recurrent disease on bone scan, and his testosterone level was normal. The faculty discuss the challenge of timing treatment in the setting of biochemical recurrence. They also highlight the crucial importance of addressing comorbidities, such as metabolic syndrome, through the management of reversible cardiovascular risk factors to better prepare patients starting androgen-deprivation therapy.
Alex K. Bryant, MD, of the University of Michigan, examined Veterans Administration (VA) facilities in which lower prostate-specific antigen (PSA) screening rates were associated with a subsequent increased incidence of metastatic prostate cancer, particularly among men aged 70 and older. From 2008 to 2019, PSA screening rates have declined in the national VA system, data that may be used to inform shared decision-making about the potential benefits of screening for those who wish to reduce their risk of advanced prostate cancer. (Abstract 298).
Rahul Aggarwal, MD, of the University of California, San Francisco, discusses recent data from the PRESTO study, which showed that apalutamide plus androgen-deprivation therapy (ADT) for 12 months significantly prolonged PSA progression-free survival compared with ADT alone in patients with biochemically recurrent prostate cancer. These results provide support for the intensification of ADT in this setting. (Abstract LBA63).
Sumanta K. Pal, MD, introduces his City of Hope colleagues, Hedyeh Ebrahimi, MD, MPH, who discusses the prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma, and Daniela Castro, MSc, who discusses expanding eligibility criteria in kidney, prostate, and urothelial cancer trials to more accurately reflect the real-world population and reducing exclusion criteria. (Abstract 662, 612, 34, 453)
Scott T. Tagawa, MD, of Weill Cornell Medicine, NewYork-Presbyterian Hospital, discusses study results showing that, the anti-PSMA (prostate-specific membrane antigen) monoclonal antibody J591 with ketoconazole and hydrocortisone, when radiolabeled with lutetium-177, leads to improved 18-month metastasis-free survival vs radiolabeling with indium-111 in patients with nonmetastatic (M0) castration-resistant prostate cancer. This supports the development of anti-PSMA radioimmunotherapy, although the optimal radionuclide and targeting agent are unknown. (Abstract LBA21).
Alan H. Bryce, MD, of the Mayo Clinic, discusses the final results of the primary endpoint of rPFS and interim results on overall survival among patients with chemotherapy-naive metastatic castration-resistant prostate cancer. The data showed that rucaparib improved radiographic progression-free survival compared with either docetaxel or abiraterone and enzalutamide in disease with BRCA1/2 alterations. (Abstract 18).
Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses phase III findings from the KEYNOTE-921 study, which was designed to assess the combination of pembrolizumab and docetaxel in the treatment of patients with metastatic castration-resistant prostate cancer. They had not received chemotherapy, but their disease progressed on the next-generation hormonal agent, or they could not tolerate the agent. (Abstract 19).
Paul L. Nguyen, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discusses results from the FORMULA-509 study, which compared postoperative salvage radiotherapy and 6 months of GnRH agonist with or without abiraterone acetate/prednisone (AAP) and apalutamide, after radical prostatectomy. The study suggested that adding AAP and apalutamide to salvage radiotherapy, plus 6 months of androgen-deprivation therapy, may improve outcomes, particularly in the subgroup of patients with a prostate-specific antigen level higher than 0.5 ng/mL. (Abstract 303).
Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, discusses phase III results from the TALAPRO-2 study, which suggested an improvement in radiographic progression-free survival with the combination of talazoparib and enzalutamide over standard-of-care enzalutamide alone as first-line treatment in patients with metastatic castration-resistant prostate cancer. The improvement was seen regardless of homologous recombination repair gene mutations. The combination regimen delayed the time to chemotherapy and worsening in global health status and quality of life. (Abstract LBA17).
Neal D. Shore, MD, of Carolina Urologic Research Center/Genesis Care, discusses new data from the ENACT trial, which showed that patients with prostate cancer and the RNA biomarkers PAM50 and AR-A were likely to have better outcomes with enzalutamide treatment. The results suggest that such RNA biomarkers may help to identify patients who may benefit from enzalutamide treatment compared with active surveillance (Abstract 1385P).
Neal D. Shore, MD, of the Carolina Urologic Research Center, discusses his study findings, showing that germline genetic testing influenced care for patients with prostate cancer. Men whose genetic test was positive for a pathogenic germline variant received more recommendations for changes to follow-up and treatment, and for testing and counseling of relatives, than did patients with negative or uncertain test results (Abstract 10500).
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Michael S. Hofman, MBBS, of Peter MacCallum Cancer Centre, University of Melbourne, discuss follow-up results on LuPSMA vs cabazitaxel in patients with metastatic castration-resistant prostate cancer progressing after docetaxel treatment. The findings suggest that LuPSMA is a suitable option for this population, with fewer adverse events, higher response rates, improved patient-reported outcomes, and similar overall survival compared with cabazitaxel (Abstract 5000).
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Ian D. Davis, PhD, MBBS, of Monash University and Eastern Health, discuss the latest findings from ANZUP Cancer Trials Group’s ENZAMET cooperative group trial of enzalutamide in patients with metastatic hormone-sensitive prostate cancer. The results corroborate the benefit of enzalutamide with improved overall survival, and involve some exploratory subgroup analyses (Abstract LBA5004).
Matthew R. Smith, PhD, MD, of Massachusetts General Hospital Cancer Center, discusses overall survival findings from the ARASENS trial, which assessed the efficacy of the androgen receptor inhibitor darolutamide vs placebo in combination with androgen-deprivation therapy and docetaxel for patients with metastatic hormone-sensitive prostate cancer (Abstract 13).
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.
In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss the role of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy in the treatment of metastatic castration-resistant prostate cancer. The patient is an 81-year-old man with 13-year history of prostate cancer who had received multiple prior lines of treatment for his metastatic disease, but no prior taxane. After his PSA rose again, he opted to travel abroad for lutetium (Lu-177) PSMA therapy, since he was not eligible for trials in the United States. The faculty discuss the VISION trial and the current and future role of PSMA-targeted radioligand therapy in prostate cancer. Editor’s Note: This video was filmed prior to the FDA approval of Lu-177 PSMA radioligand therapy on March 23, 2022.
This is Part 3 of Updates in Prostate Cancer, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss the first-line therapy for BRCA2-mutated metastatic castration-resistant prostate cancer. The patient is a 69-year-old man with new castration-resistant prostate cancer who was previously treated with androgen-deprivation therapy plus docetaxel for metastatic hormone-sensitive prostate cancer and has a known BRCA2 mutation. The faculty discuss their choices for first-line therapy for this patient, reviewing the current NCCN recommendations, the role of PARP inhibitors, and recent data from the PROpel and MAGNITUDE trials.
This is Part 2 of Updates in Prostate Cancer, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss doublet and triplet androgen-deprivation therapy options for metastatic prostate cancer. The patient is a 71-year-old man with metastatic prostate cancer, a PSA of 275, and a positive bone scan, who has begun to receive androgen-deprivation therapy. The faculty discuss what, if any, additional therapy they might add to this patient’s treatment regimen, weighing the current doublet and triplet combination options for metastatic hormone-sensitive prostate cancer. They review the results of the recent PEACE-1 and ARASENS trials and emphasize the importance of assessing bone mineral density and of encouraging genetic counseling for these patients.
This is Part 1 of Updates in Prostate Cancer, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. �In this video, Drs. Celestia (Tia) Higano, Julie Graff, and Neal Shore discuss the management of metastatic hormone-sensitive prostate cancer in elderly patients. The patient is a fit 88-year-old man with a history of localized prostate cancer who was originally treated with stereotactic body radiation therapy and is reluctant to start androgen-deprivation therapy for his metastatic disease due to the potential side effects. The faculty discuss the importance of counseling patients about side effects of treatment and when to consider androgen-deprivation therapy rather than metastasis-directed therapy alone, reviewing the results of the phase III HERO trial.
Julio M. Pow-Sang, MD, of Moffitt Cancer Center, discusses the treatment landscape for localized prostate cancer and its heterogeneity, the critical importance of stratifying risk to determining treatment options, and the continued improvement of therapy in the field.
Xin Gao, MD, of Massachusetts General Hospital, discusses phase I/II findings on bavdegalutamide, an androgen receptor protein degrader, which showed clinical activity in heavily pretreated patients with metastatic castration-resistant prostate cancer who received one to two prior novel hormonal agents.
Tanya B. Dorff, MD, of City of Hope National Medical Center, discusses the first-in-human phase I findings showing that prostate stem cell antigen (PSCA) CAR T-cell therapy is feasible in patients with metastatic castration-resistant prostate cancer, with preliminary antitumor activity exhibited.
Neil E. Fleshner, MD, MPH, of the Princess Margaret Cancer Centre, discusses phase II results from the ACDC-RP trial, which indicate a significant tumor response to neoadjuvant abiraterone acetate plus prednisone and leuprolide, with or without cabazitaxel, in patients with high-risk prostate cancer. Those who exhibited either a complete response or minimal residual disease experienced higher rates of progression-free survival. According to Dr. Fleshner, genomic efforts are underway to determine predictors of response.
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses some key research developments in kidney cancer, including data on nivolumab and ipilimumab with or without CBM588 in metastatic renal cell carcinoma; intestinal microbiome associated with the development of grade 3 or 4 adverse events in patients with metastatic disease who have been treated with nivolumab plus ipilimumab and probiotic support; the link between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer; mutations in the androgen receptor gene in patients with prostate cancer receiving novel androgen deprivation treatments; and findings on waning antibody titers in patients who have received COVID-19 vaccinations (Roundup of Abstracts 371, 561, 374, Posters 38 and 48).