Expert opinions on mCRPC management

Emerging pharmacological strategies that could help meet unmet needs in mCRPC

Professor Merseburger (University Hospital Schleswig-Holstein, Germany) reflects on the role of investigational treatments that do not rely on the patient’s biomarker status for meeting unmet needs in mCRPC management.

Clinical barriers to uptake of clinical practice guidelines for mCRPC

Professor Merseburger considers why uptake of clinical practice guideline recommendations for mCRPC management remains low.

What is the most important factor for patient populations in mCRPC trials?

According to Professor Agarwal (Huntsman Cancer Institute, University of Utah, USA), the most important factor to consider for the patient population in phase 3 first-line mCRPC trials relates to evidence of disease progression when patients on novel hormonal therapy “reach the mCRPC space”.

Differences in clinical trial design for PARP inhibitors and novel hormonal therapies

Professor Agarwal outlines three trials that investigated PARP inhibitors for mCRPC (MAGNITUDE, PROPEL, TALAPRO-2) and analyses similarities and differences (minor and major) in the design of these trials.

Meet the experts

Axel Merseburger

Axel Merseburger is Professor of Urology and Chairman of the Department of Urology at University Hospital Schleswig-Holstein, Campus Lübeck, Germany. His research includes molecular and clinical aspects of uro-oncology, with specific interest in biomarkers and prognostic factors for prostate cancer, renal cell carcinoma and transitional cell carcinoma. He has authored and co-authored >300 peer-reviewed articles and he is the principal investigator in Phase 2 and 3 clinical trials within urologic oncology. Professor Merseburger is the chairman elect for the European Scholarship Program (ESUP) of the European Association of Urology (EAU) and is Editor-in-Chief of the European Journal of Haematology and Oncology and Aktuelle Urologie.

Disclosures: Lectures/Speaker/Honoraria: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Ferring, Ipsen, MSD, Merck Serono, Janssen, Takeda, TEVA, Astellas, Novartis, Pfizer, Recordati, Roche.

Consultancy: AstraZeneca, Astellas, Bayer, Bristol-Myers Squibb, Ferring, Ipsen, Janssen, EUSAPharm, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer, Recordati, Roche.

Research and clinical trials: AstraZeneca, Astellas, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, EUSAPharm, MSD, Merck Serono, Novartis, Takeda, Teva, Pfizer, Roche.

Neal Shore

Neal Shore, MD, FACS, is the Medical Director for the Carolina Urologic Research Center and the Chief Medical Officer, Strategic Growth and Pharmacy, GenesisCare, USA.

Dr Shore has conducted more than 400 clinical trials, focusing mainly on genitourinary oncology. He serves on the Society for Immunotherapy of Cancer (SITC) Guidelines Committee for Bladder Cancer, as well as the boards of the Bladder Cancer Advocacy Network, Maple Tree Alliance, and the Duke Global Health Institute. He is the Chair of both the Prostate Cancer Academy and the Bladder/Kidney Cancer Academy for LUGPA/Specialty Network.

Disclosures: AbbVie, Alessa Therapeutics, Alkido Pharma, Amgen, Arquer Diagnostics, Asieris, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, Ferring, Foundation Medicine, GC Oncology, Genentech, GenesisCare, Guardant Health, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, Mdxhealth, Merck, Minomic, Myovant Sciences, Myriad, NGM Bio, Nonagen Bioscience, Novartis, Nymox Pharmaceutical Corporation, Pacific Edge, Pfizer, Photocure, PlatformQ, Profound Pharma, Promaxo, Propella Therapeutics, Protara Therapeutics, Sanofi, Sesen Bio, Speciality Networks, Telix, Tolmar, UroGen Pharma, Vaxiion Therapeutics, and Vessi Medical

Karim Fizazi

Karim Fizazi is a medical oncologist at Institut Gustave Roussy and Professor in Oncology at the Université Paris-Saclay, France. He has published more than 400 peer-reviewed articles. In 2010, Fizazi demonstrated the role of denosumab for the prevention of complications of bony metastases from prostate cancer, such as fractures or major pain. In the GETUG-12 trial, published in 2015, Prof. Fizazi was the first to establish the role of early chemotherapy to prevent relapse in men with localised prostate cancer at high risk for relapse. He is the chair of two major pivotal trials testing next-generation androgen receptor axis targeting agents:

• LATITUDE, which demonstrated in 2017 the impact of abiraterone on survival in men with de novo metastatic prostate cancer
• ARAMIS, which showed overall survival improvement with darolutamide, a drug first tested by Fizazi in Phase 1 trials in men with non-metastatic castrate-resistant prostate cancer

To push forward clinical research on prostate cancer in Europe, in 2013, Fizazi created the Prostate Cancer Consortium in Europe (PEACE). He leads three large PEACE European academic Phase 3 trials: PEACE-1 (testing abiraterone and radiotherapy to local primary cancer in de novo metastatic prostate cancer), which has completed accrual, the currently ongoing PEACE-2 trial (testing cabazitaxel and pelvic radiotherapy in very high-risk localised prostate cancer), and PEACE-4, which is testing the role of aspirin and statins in castrate-resistant prostate cancer.

Disclosures: Participation in advisory boards and talks for Amgen, Arvinas, Astellas, Astrazeneca, Bayer, Clovis, CureVac, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Orion, Pfizer, Sanofi.

Honoraria to Gustave Roussy.

Neeraj Agarwal

Neeraj Agarwal is a professor of medicine and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute (HCI), University of Utah, USA. He also directs the Genitourinary Oncology (GU) Program, and the Center of Investigational Therapeutics (CIT) at the HCI.

Dr Agarwal serves as a panel member for the NCCN guideline committees for bladder and kidney cancers. He is an advisor to the Oncology Drug Advisory Committee and the United States Food and Drug Administration and leads early therapeutics in the SWOG genitourinary cancers committee. He holds numerous scientific communications leadership roles, including editorial board member of several journals, such as the Journal of Clinical Oncology and European Urology. He also serves as a member of the ASCO Genitourinary Cancers Advisory Panel.

Disclosures: Consultancy: Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics.

Research funding: Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, Tracon.

Elena Castro

Dr Elena Castro is a Consultant Medical Oncologist in GU tumours at the Virgen de la Victoria University Hospital in Malaga, Spain, where she leads the GU cancers translational research unit as part of the Malaga Biomedical Research Institute (IBIMA). Dr Castro’s research is focused on the clinical and molecular characterisation of BRCA2 mutations, and other DNA repair defects in prostate cancer. She is actively involved in several projects that identify and validate biomarkers to optimise prostate cancer treatments. Dr Castro has acted as Principal Investigator for several clinical trials in prostate cancer, whilst authoring numerous articles in esteemed peer-reviewed journals, including Nature, Journal of Clinical Oncology, and European Urology. 

Disclosures: Honoraria or consultation fees: AstraZeneca, Bayer, Daiichi-Sankyo, Janssen, Lilly, Medscape, Merck, MSD, Novartis, Pfizer. 

Grants and research support: Bayer (inst), Janssen (inst), Pfizer (inst).

Speaker fees: AstraZeneca, Astellas, Bayer, Janssen, Novartis, Pfizer, Sandoz, Telix.

Travel support: AstraZeneca, Janssen, Pfizer.

Professor Silke Gillessen

Professor Silke Gillessen is a medical oncologist with a focus on genitourinary cancer. She is the Genitourinary Cancer Systemic Therapy Research Chair at the University of Manchester, UK, Honorary Consultant at The Christie Hospital in Manchester, and works as a consultant in the Department of Oncology/Haematology at the Kantonsspital St. Gallen, Switzerland. Professor Gillessen is also Head of the Department of Medical Oncology, full professor at the Università della Svizzera Italiana (USI) in Lugano and Director of the Oncology Institute of Southern Switzerland (IOSI) in Bellinzona, Switzerland.

Disclosures: Consultation/speaking/travel fees from AAA International, Amgen, AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, InnoMedica, Ipsen, Meister-ConCept, Modra Pharmaceuticals, MSD, Myriad Genetic, Novartis, Orion, Pfizer, Roche, and Telix Pharmaceuticals.

Patent for a research method for biomarker WO2009138392.