Lack of consensus identifies important areas for future clinical research: Advanced Prostate Cancer Consensus Conference (APCCC) 2019 findings.

BACKGROUND

Innovations in treatments, imaging and molecular characterisation have improved outcomes for people with advanced prostate cancer; however, many aspects of clinical management are devoid of high-level evidence. At the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, many of these topics were addressed, and consensus was not always reached. The results from clinical trials will most reliably plus the gaps.

METHODS

An invited panel of 57 experts voted on 123 multiple-choice questions on clinical management at APCCC 2019. No consensus was reached on 88 (71.5%) questions defined as <75% of panellists voting for the same answer option. We reviewed clinicaltrials.gov to identify relevant ongoing phase III trials in these areas of non-consensus.

RESULTS

A number of ongoing phase III trials were identified that are relevant to these non-consensus issues. However, many non-consensus issues appear not to be addressed by current clinical trials. Of note, no phase III but only phase II trials were identified, investigating side effects of hormonal treatments and their management.

CONCLUSIONS

Lack of consensus almost invariably indicates gaps in existing evidence. The high percentage of questions lacking consensus at APCCC 2019 highlights the complexity of advanced prostate cancer care and the need for robust, clinically relevant trials that can fill current gaps with high-level evidence. Our review of these areas of non-consensus and ongoing trials provides a useful summary, indicating areas in which future consensus may soon be reached. This review may facilitate academic investigators to identify and prioritise topics for future research.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Ursula Vogl: Advisory role (institutional): Janssen, Astellas, Merck, MSD, Pfizer, Roche, Bayer, BMS. Travel support: Janssen; Speakers Bureau (compensated, institutional): Janssen, Astellas, Pfizer, Roche, SAMO, BMS. Tomasz M Beer: Consulting for: Arvinas, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squib, Constellation, Grail Inc., Janssen, Myovant Sciences, Pfizer, Sanofi, Clovis Oncology, Novartis, Tolero; Research funding paid to Institution: Alliance Foundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc./Advanced Accelerator Applications (AAA), Freenome, Grail Inc., Harpoon Therapeutics, Janssen Research & Development, Medivation Inc., Sotio, Theraclone Sciences/Onco Response, Zenith Epigenetics, Stock Ownership: Arvinas Inc., Salarius Pharmaceuticals. Ian D Davis: Advisory boards within last 2 years (all honoraria to ANZUP): Astellas, AstraZeneca, Bayer, Eisai, Ipsen, Janssen, Merck/MSD, Pfizer, Roche; Research funding (trial funding to Eastern Health or ANZUP): Amgen, Astellas, AstraZeneca, Bayer, BMS, Eisai, Exelixis, Janssen, Medivation, Movember, MSD, Pfizer, Roche/Genentech, Seagen. Company board (unremunerated): ANZUP Cancer Trials Group; Funding support: Employers (Monash University, Eastern Health). Neal D Shore: Research/Consulting/Advisory Boards: AbbVie, Astellas, Astra Zeneca, Bayer,BMS, Dendreon, Exact Imaging, Exct Sciences, Ferring, Foundtion Medicine, Guardant, Janssen, Merck, Myovant,Novartis, Nymox, Pierian Dx, Phosphorous, Pfizer, Sanofi, Tolmar. Christopher J Sweeney: Consulting or Advisory Role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, Pfizer, Lilly, Research Funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); Patents, Royalties, Other Intellectual Property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination. Stock or Other Ownership: Leuchemix; Piet Ost(:) Institutional receipt of grants/research supports: Merck, Bayer, Ferring, Varian; Receipt of honoraria or consultation fees (institution): Astellas, Bayer, Curium Ferring, Janssen, Novartis, Sanofi, Sandoz. Gerhardt Attard: Dr Attard reports personal fees, research support and travel support from Janssen; personal fees and/or travel support from Astellas, Pfizer, Millennium Pharmaceuticals, Ipsen, Ventana, Veridex, Novartis, Abbott Laboratories, ESSA Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Takeda and Sanofi Aventis and research funding from AstraZeneca, Innocrin Pharma and Arno Therapeutics; in addition, Dr Attard's former employer, The Institute of Cancer Research (ICR), receives royalty income from abiraterone acetate and Dr Attard receives a share of this income through ICR's Rewards to Discoverers Scheme. Charles G Drake: Employee of Janssen Research, Springhouse PA, USA. Eleni Efstathiou: Ad Board/steering committee/research support/honoraria Bayer, Janssen, Astellas, Pfizer, MSD, Sanofi, Astra Zeneca, ORIC. Karim Fizazi: Participation to advisory boards or symposium for Amgen, Astellas, Bayer, Janssen, Sanofi, AstraZeneca with payments to my institution. Participation to advisory boards for CureVac and Orion with personal honoraria. Nicolas James: Trial funding from: Cancer Research UK, Medical Research Council, Astellas, Janssen, Novartis, Pfizer, Sanofi Aventis; Speaking fees and Advisory Boards: AAA, a Novartis company, Astellas, Astra Zeneca, Bayer, Clovis, Ferring, Janssen, Merck, Novartis, Pfizer, Sanofi Aventis. Nicolas Mottet: Receipt of grants/research supports: Astellas, Sanofi Pasteur; Receipt of honoraria or consultation fees: Astellas, Jansen, BMS, Bayer, IPSEN, Ferring, Sanofi, Astra Zeneca, Carrik, Arquer diagnostics, Mark Rubin: funding: Janssen, Roche, Novartis; patients: listed as co-inventor on patents in the diagnostic and treatment fields for ETS fusions (Harvard/Michigan), EZh2 (Michigan), SPOP (Cornell) and AURKA/NMYC (Cornell), SWI/SNF, Scientific Board of Advisors: NeoGenomics Labs. Oliver Sartor: Consultant: Advanced Accelerator Applications (AAA), Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen Technologien Meunchen, Janssen, Merck, Moyvant, Myriad, Noria Therapeutics, Inc., Novartis, Noxopharm, Progenics, POINT Biopharma, Pfizer, Sanofi, Tenebio, Telix, Theragnostics; Grant/Research, Support: Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Constellation, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, Tenebio. Eric Small: Stock: Fortis Therapeutics (Recipient: Dr. Small), Harpoon Therapeutics (Recipient: Dr. Small), Teon Therapeutics (Recipient: Dr. Small). Honoraria for Speaking Engagements, Janssen, 8/2020 Janssen China, PC Summit, 8/2020 Janssen South Africa, Promotional Speaker, 6/2021 Janssen Portugal, 12/2020Janssen Japan, 2/2021 Janssen Spain. J&J, 7/2020 Saudi Arabia, 7/2020 J&J Magnitude Steering Committee, 9/2020 UAE/Qatar. Consulting/Advisory Board (Compensated), Janssen (ongoing), Fortis (ongoing), Teon Therapeutics: 12/2019 SAB, 7/27/2020, 8/2020 Protocol Review. Matthew R Smith: advisory boards: Amgen, Astellas, Bayer, Janssen, Pfizer, Lilly; consultant: Amgen, Astellas, Bayer, Janssen, Pfizer, Lilly; Sponsored research (support to institution for clinical trials): Amgen, Arvinas, Bayer, ESSA, Janssen, Pfizer, Lilly. Matthew R Sydes(:) Prof Sydes reports grants and non-financial support from Astellas, grants from Clovis, grants and non-financial support from Janssen, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Sanofi; these are all outside this project directly but these grants to the institution do support some of the trials listed in the manuscript. Prof Sydes also reports personal fees from Lilly Oncology and from Janssen for clinical trial statistics training meetings for clinicians (studiously avoiding discussion of particular drugs). Bertrand Tombal: Paid consultant, adviser, or investigator for Amgen, Astellas, Bayer, Ferring, Janssen, Myovant, Pfizer, Sanofi. Piet Ost: Institutional receipt of grants/research supports: Merck, Bayer, Ferring, Varian Receipt of honoraria or consultation fees (institution): Astellas, Bayer, Curium Ferring, Janssen, Novartis, Sanofi, Sandoz. Johann de Bono has served on advisory boards and received fees from many companies including Amgen, Astra Zeneca, Astellas, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech/Roche, Genmab, GSK, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Menarini/Silicon Biosystems, Orion, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals. He is an employee of The ICR, which have received funding or other support for his research work from AZ, Astellas, Bayer, Cellcentric, Daiichi, Genentech, Genmab, GSK, Janssen, Merck Serono, MSD, Menarini/Silicon Biosystems, Orion, Sanofi Aventis, Sierra Oncology, Taiho, Pfizer, Vertex, and which has a commercial interest in abiraterone, PARP inhibition in DNA repair defective cancers and PI3K/AKT pathway inhibitors (no personal income). He was named as an inventor, with no financial interest, for patent 8,822,438. He has been the CI/PI of many industry sponsored clinical trials. JDB is a National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Aurelius Omlin: Advisory role (compensated, institutional): Astra Zeneca, Astellas, Bayer, Janssen, Molecular Partners, MSD, Pfizer, Roche, Sanofi Aventis; Research support (institutional): TEVA, Janssen Travel support: Astellas, Bayer, Janssen, Sanofi Aventis; Speakers Bureau (compensated, institutional): Bayer, Astellas. Silke Gillessen: received personal honoraria for participation in advisory boards for Sanofi, Orion, Roche, Amgen, MSD; other honoraria from RSI (Televisione Svizzera Italiana); invited speaker for ESMO, SAKK, SAMO, Orikata, CACA-GU; Speaker's bureau for Janssen Cilag; travel grant from ProteoMEdiX; institutional honoraria for advisory boards for Bayer, Janssen Cilag, Roche, AAA International including IDMC and Steering Committee, Amgen-Steering Committee, Menarini Silicon Biosystems, Astellas Pharma, Tolero Pharmaceuticals, MSD, Pfizer, Telixpharma, BMS and Orion; patent, royalties, other intellectual property method for biomarker WO2009138392. Alberto Bossi, Susan Halabi, Howard R Soule, Anwar R Padhani, Stefano Fanti, Mark Roach(:) have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.