Addressing Current Questions Related to Novel Treatment Approaches for Urothelial Bladder Cancer and Prostate Cancer — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This program is intended for medical and radiation oncologists, urologists and other healthcare providers involved in the treatment of bladder and prostate cancers.

LEARNING OBJECTIVES

• Recognize the incidence of nectin-4 expression in urothelial bladder cancer (UBC), and appreciate the scientific justification for the development of antibody-drug conjugates (ADCs) targeting this novel biomarker.
• Interrogate published efficacy and safety findings with anti-PD-1/PD-L1 antibodies in combination with ADC therapy as first-line treatment for metastatic UBC, and consider the current role of this strategy.
• Review available research findings with HER2-directed ADCs for patients with advanced UBC, and optimally integrate these novel agents into management algorithms.
• Appraise published research on the optimal management of biochemical recurrence after local treatment for prostate cancer, and counsel appropriate patients about the potential benefits of FDA-approved systemic treatment options.
• Explore available data with treatment intensification with cytotoxic therapy, secondary hormonal therapy or combinations of these approaches for metastatic hormone-sensitive prostate cancer, and effectively integrate these strategies into clinical management algorithms.
• Assess the available research database supporting the use of PARP inhibitors in combination with androgen receptor pathway inhibitors for patients with metastatic castration-resistant prostate cancer harboring a homologous recombination repair gene alteration, and discern the current role of this treatment approach.
• Recall the design of ongoing clinical trials evaluating novel ADCs for advanced UBC or hormonal therapy-based approaches for prostate cancer, and counsel appropriate patients about availability and participation.

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HOW TO USE THIS CME ACTIVITY

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CME credit is no longer available for this issue

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FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Neeraj Agarwal, MD, FASCO
Professor of Medicine
Senior Director for Clinical Research
Huntsman Cancer Institute Presidential Endowed Chair of Cancer Research
Director, Center of Investigational Therapeutics
Director, Genitourinary Oncology Program
Huntsman Cancer Institute, University of Utah (NCI-CCC)
Salt Lake City, Utah

No relevant conflicts of interest to disclose.

Andrew J Armstrong, MD, ScM
Professor of Medicine, Surgery, Pharmacology and Cancer Biology
Director of Research
Duke Cancer Institute Center for Prostate and Urologic Cancers
Divisions of Medical Oncology and Urology
Duke University
Durham, North Carolina

Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Cytogen Corporation, Janssen Biotech Inc, Merck, Myovant Sciences, Novartis, Pfizer Inc; Consulting Agreements: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Curium, Janssen Biotech Inc, Merck, Novartis, Pfizer Inc; Contracted Research: Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Janssen Biotech Inc, Merck, Novartis, Pathos, Pfizer Inc.

Terence Friedlander, MD
Professor of Medicine and Robert and Virginia O’Reilly Family Endowed Chair
Chief, Division of Hematology/Oncology
Zuckerberg San Francisco General Hospital
Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
San Francisco, California

Advisory Committees: Aadi Bioscience, AbbVie Inc, Adaptimmune, Aktis Oncology, Astellas, Bicycle Therapeutics, Bristol Myers Squibb, Gilead Sciences Inc, Merck, Pfizer Inc, Samsung Bioepis; Consulting Agreements: Astellas, EMD Serono Inc, Pfizer Inc; Contracted Research: Bicycle Therapeutics, Genentech, a member of the Roche Group, Johnson & Johnson Pharmaceuticals, Pfizer Inc; Data and Safety Monitoring Boards/Committees: Bicycle Therapeutics.

Matthew D Galsky, MD
Professor of Medicine
Icahn School of Medicine at Mount Sinai
Co-Leader, Bladder Cancer Center of Excellence
Associate Director, Translational Research
The Tisch Cancer Institute
New York, New York

Advisory Committees: AbbVie Inc, Aktis Oncology, Alligator Bioscience, Analog Devices Inc, Asieris Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Basilea Pharmaceutica Ltd, Bicycle Therapeutics, Bristol Myers Squibb, Curis Inc, Daiichi Sankyo Inc, Dragonfly Therapeutics, EMD Serono Inc, FUJIFILM Pharmaceuticals USA Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Janssen Biotech Inc, Merck, Numab Therapeutics AG, Pfizer Inc, Rappta Therapeutics, Seagen Inc, Silverback Therapeutics, UroGen Pharma, Veracyte Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Dendreon Pharmaceuticals Inc, Genentech, a member of the Roche Group, Merck, Novartis.

MODERATOR
Elisabeth I Heath, MD
Chair, Department of Oncology
Mayo Clinic
Rochester, Minnesota

Advisory/Consulting: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Sanofi; Honoraria/Paid Travel: Astellas, Bayer HealthCare Pharmaceuticals, Caris Life Sciences, Sanofi, Seagen Inc; Institutional Research Support: Amgen Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BioXcel Therapeutics Inc, Bristol Myers Squibb, Calithera Biosciences, Caris Life Sciences, Corcept Therapeutics, Corvus Pharmaceuticals, Daiichi Sankyo Inc, Eisai Inc, Exelixis Inc, F Hoffman-La Roche Ltd, Fortis Therapeutics, Gilead Sciences Inc, GSK, Harpoon Therapeutics, Infinity Pharmaceuticals Inc, iTeos Therapeutics, Janssen Biotech Inc, Merck, Mirati Therapeutics Inc, Modra Pharmaceuticals, MSD, Novartis, Oncolys BioPharma, Peloton Therapeutics Inc, a wholly-owned subsidiary of Merck & Co Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, POINT Biopharma, Seagen Inc; Steering Committees: Janssen Biotech Inc; Speakers Bureaus: Sanofi; Nonrelevant Financial Relationships: Calibr-Skaggs Institute for Innovative Medicines.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantor.

These activities are supported by an educational grant from Astellas and Pfizer Inc.

Release date: March 2025
Expiration date: March 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Urothelial Bladder Cancer

Dr Friedlander

O’Donnell PH et al. Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer. J Clin Oncol. 2023 Sep 1;41(25):4107-17. Abstract

Powles T et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). Genitourinary Cancers Symposium 2025;Abstract 664.

Powles T et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 2024;390(10):875-88. Abstract

Powles T et al. EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). ESMO 2023;Abstract LBA6.

Powles T et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 2021;384(12):1125-35. Abstract

Rosenberg JE et al. Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. ASCO 2022;Abstract 4516.

Rosenberg JE et al. Study EV-103 cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC). ESMO 2022;Abstract LBA73.

 

Dr Galsky

Aggen DH et al. HER2 and PD-L1 immunohistochemistry (IHC) expression, and HER2 genomic alterations: Associations and clinical outcomes for advanced bladder cancer. Genitourinary Cancers Symposium 2024;Abstract 538.

Galsky MD et al. Preliminary efficacy and safety of disitamab vedotin (DV) with pembrolizumab (P) in treatment (Tx)-naive HER2-expressing, locally advanced or metastatic urothelial carcinoma (la/mUC): RC48G001 cohort C. ESMO 2024;Abstract 1967MO.

Galsky MD et al. Phase 2 multi-cohort clinical study evaluating disitamab vedotin alone and in combination with pembrolizumab in patients with HER2-expressing unresectable or metastatic urothelial carcinoma (RC48G001, trial in progress). SITC 2022;Abstract 663.

Galsky MD et al. Primary analysis from DS8201-A-U105: A phase 1b, 2-part, open-label study of trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing urothelial carcinoma (UC). Genitourinary Cancers Symposium 2022;Abstract 438.

Grivas P et al. Sacituzumab govitecan in combination with pembrolizumab for patients with metastatic urothelial cancer that progressed after platinum-based chemotherapy: TROPHY-U-01 cohort 3. J Clin Oncol 2024;42(12):1415-25. Abstract

Hamilton E et al. Trastuzumab deruxtecan with nivolumab in HER2-expressing metastatic breast or urothelial cancer: Analysis of the phase Ib DS8201-A-U105 study. Clin Cancer Res. 2024;30(24):5548-58. Abstract

Li BT et al. Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): An international, phase 2 study. Lancet Oncol 2024;25(6):707-19. Abstract

Li BT et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with solid tumors harboring specific HER2-activating mutations (HER2m): Primary results from the international phase II DESTINY-PanTumor01 (DPT-01) study. ESMO 2023;Abstract 654O.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Meric-Bernstam F et al. Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: Primary analysis from the DESTINY-PanTumor02 (DP-02) study. ESMO 2023;Abstract LBA34.

O’Donnell PH et al. Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer. J Clin Oncol 2023;41(25):4107-17. Abstract

Rosenberg JE et al. EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. Ann Oncol 2023;34(11):1047-54. Abstract

Sheng X et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma: A Combined analysis of two phase II clinical trials. J Clin Oncol 2024;42(12):1391-402. Abstract

Sheng X et al. RC48-ADC for metastatic urothelial carcinoma with HER2-positive: Combined analysis of RC48-C005 and RC48-C009 trials. ASCO 2022;Abstract 4520.

Xu H et al. A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. ASCO 2022;Abstract 4519.

Zhou L et al. Disitamab vedotin (DV) plus toripalimab (T) in unresectable locally advanced or metastatic urothelial carcinoma (la/mUC): Long-term outcomes from a phase Ib/II study. ESMO 2024;Abstract 1979P.

 

Prostate Cancer

Dr Armstrong

Armstrong AJ et al. The efficacy of enzalutamide plus androgen deprivation therapy in oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. Eur Urol 2023;84(2):229-41. Abstract

Armstrong AJ et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2022;40(15):1616-22. Abstract

Attard G et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: A meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet 2022;399(10323):447-60. Abstract

Attard G et al. Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol. ESMO 2022;Abstract LBA62.

Freedland SJ et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med 2023;389(16):1453-65. Abstract

Hussain M et al. Darolutamide plus androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer by disease volume and risk subgroups in the phase III ARASENS trial. J Clin Oncol 2023;41(20):3595-607. Abstract

McManus HD, Armstrong AJ. The past, present, and future of treatment intensification for metastatic hormone-sensitive prostate cancer. J Clin Oncol 2023;41(20):3576-9. Abstract

Merseburger AS et al. Targeted investigational treatment analysis of novel anti-androgen (TITAN) study: Ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy. BJU Int 2024;134(6):982-91. Abstract

Smith MR et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 2022;386(12):1132-42. Abstract

Smith MR et al. Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial. Genitourinary Cancers Symposium 2022;Abstract 13.

Sweeney CJ et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015;373(8):737-46. Abstract

Tang C et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer: The EXTEND phase 2 randomized clinical trial. JAMA Oncol 2023;9(6):825-34. Abstract

 

Dr Agarwal

Agarwal N et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. Genitourinary Cancers Symposium 2025;Abstract LBA18.

Agarwal N et al. EvoPAR-Prostate01: Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with new hormonal agents in patients with mCSPC +/- HRR mutations. AUA 2024.

Agarwal N et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomised, placebo-controlled, phase 3 trial. Lancet 2023;402(10398):291-303. Abstract

Agarwal N et al. Talapro-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus enza in patients with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC). Genitourinary Cancers Symposium 2022;Abstract TPS 221.

Chi KN et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol 2023;41(18):3339-51. Abstract

Chi KN et al. Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Three-year update and final analysis (FA) of MAGNITUDE. ESMO 2023;Abstract LBA85.

Chi KN et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: Second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol 2023;34(9):772-82. Abstract

Chi KN et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Genitourinary Cancers Symposium 2022;Abstract 12.

Clarke NW et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid 2022;1(9). Abstract

Fizazi K et al. First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: The phase 3 TALAPRO-2 trial. Nat Med 2024;30(1):257-64. Abstract

Hussain M et al. BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). Genitourinary Cancers Symposium 2024;Abstract 19.

Rathkopf DE et al. AMPLITUDE: A study of niraparib in combination with abiraterone acetate plus prednisone (AAP) versus AAP for the treatment of patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC). Genitourinary Cancers Symposium 2021;Abstract TPS176.

Saad F et al. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): Final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(10):1094-108. Abstract

Swami U et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States. Cancers (Basel) 2021;13(19):4951. Abstract