1835P - A prospective study to determine the prevalence of DNA repair defects in patients (pts) with advanced prostate cancer (PC)

Background

Up to 30% of pts with advanced PC have homologous recombination repair (HRR) gene alterations. Pts with HRR gene alterations (HRR+), particularly those with BRCA gene alterations, have poor outcomes with standard of care therapies and may benefit from PARP inhibitor treatment. PREVALENCE (NCT03871816) prospectively evaluated the frequency of HRR+ in metastatic castration sensitive and castration resistant prostate cancer (mCSPC/mCRPC) pts.

Methods

In this multicenter, international study across 319 sites in 25 countries, mCSPC and mCRPC pts aged ≥18 consented to specimen collection (eg, saliva, blood, archival tumor) for germline, tumor tissue, and/or ctDNA testing. HRR genes of interest included ATM, BRCA1, BRCA2, CHEK2, CDK12, BRIP1, FANCA, HDAC2, PALB2, RAD51B, and RAD54L. PREVALENCE test results were also used to assess biomarker eligibility for niraparib interventional studies: MAGNITUDE (NCT03748641) and AMPLITUDE (NCT04497844).

Results

14598 pts enrolled between April 2019 and October 2022. Of 14073 pts who had at least one result by any assay, 1972 (14.0%) pts had at least 1 mutation in the HRR genes of interest; BRCA gene alterations were the most common, occurring in 756 pts (5.4%). 7%, 22%, and 11.5% of pts who had a test result by germline, tumor tissue and ctDNA, respectively, had at least 1 HRR gene alteration. The frequency of HRR+ was similar in mCSPC and mCRPC. Of the pts who did not have at least one result by any assay, 143 pts (1%) had no specimens submitted and 382 pts (2.6%) failed testing by all assays. Test failure rate was highest in tumor tissue (24.1%), followed by germline (3.2%) and ctDNA (2.4%).

Table: 1835P

^#Unknown mCSPC/mCRPC: n=529 ^∗Includes BRCA1/2 and BRCA co-occurring with other HRR genes ⁺Includes non-BRCA co-occurring

Conclusions

In a study of over 14000 pts with advanced PC, 14% had at least 1 HRR gene alteration; BRCA gene alteration was most common. The frequency of HRR+ was highest in pts tested by tumor tissue. PREVALENCE demonstrates the feasibility of prospective genetic testing to identify PC pts who benefit most from a precision oncology approach.

Clinical trial identification

NCT03871816.

Editorial acknowledgement

Legal entity responsible for the study

Janssen Research & Development, LLC.

Funding

Janssen Research & Development, LLC.

Disclosure

S.K. Sandhu: Financial Interests, Institutional, Advisory Board, I have served on advisory boards for BMS. The contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: BMS; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for MSD. The e contracts for my role are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Merck Sharp and Dohme; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for AstraZeneca. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: AstraZeneca; Financial Interests, Institutional, Advisory Board, I have served on advisory boards for Novartis. The contracts for my role as an advisor are set up with the institution and the funds go to a research fund at Peter MacCallum Cancer Centre: Novartis; Financial Interests, Institutional, Advisory Board, I have served on an advisory board for Merck Serono. The contracts for my service are set up with the institution and funds go into a research fund at the Peter MacCallum Cancer Centre: Merck Serono; Financial Interests, Institutional, Research Grant, My institution receives grant funding to run an investigator initiated trial that I lead: Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, Merck Sharp and Dohme; Financial Interests, Institutional, Funding, Pfizer are providing funding to my institution for the conduct of an investigator initiated clinical trial: Pfizer; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Janssen sponsored studies and don't receive any renumeration for this: Janssen; Non-Financial Interests, Principal Investigator, I am a principal investigator on several Novartis sponsored studies and don’t receive any renumeration for this: Novartis; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of Genentech sponsored studies and don't receive any renumeration for this: Genentech; Non-Financial Interests, Principal Investigator, I am a principal investigator on several of BMS sponsored studies and don't receive any renumeration for this: BMS; Non-Financial Interests, Other, I serve on the Independent Safety and Data Monitoring committee for 2 of Novartis sponsored studies and don’t receive any compensation for this: Novartis; Non-Financial Interests, Principal Investigator, I am the Principal Investigator for several AstraZeneca sponsored studies and am not remunerated for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for several Janssen sponsored trials and I do not receive compensation for this: Janssen; Non-Financial Interests, Other, I serve on the steering committee for one AstraZeneca sponsored trial and I do not receive compensation for this: AstraZeneca; Non-Financial Interests, Other, I serve on the steering committee for one Genentech sponsored trials and I do not receive compensation for this: Genentech; Non-Financial Interests, Other, I serve on the steering committee for a BMS sponsored trial and I do not receive renumeration for this: BMS. G. Gotto: Financial Interests, Advisory Board: Astellas, AstraZeneca, Bayer, EMD Serono, Ferring, Janssen, Merck, Novartis; Financial Interests, Expert Testimony: Janssen; Financial Interests, Speaker, Consultant, Advisor: Astellas, AstraZeneca, Bayer, EMD Serono, Ferring, Janssen, Merck, Tolmar. F.E. Vera-Badillo: Financial Interests, Research Funding: Janssen; Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, AAA, Bayer, Janssen, Merck. S. Byun: Financial Interests, Principal Investigator: Janssen, Pfizer, Astellas, MSD, Bayer, AstraZeneca; Financial Interests, Speaker, Consultant, Advisor: Janssen, Astellas, Bayer, AstraZeneca. H.J. Cutuli: Financial Interests, Personal, Invited Speaker, SPEAKER PROSTATE CANCER HORMONOSENSITIVE: Bayer; Financial Interests, Personal, Advisory Board: MSD, Astellas; Financial Interests, Personal, Advisory Board, CASE REPORT: Janssen; Financial Interests, Personal and Institutional, Local PI, PHASE 2 AND PHASE 3 CLINICAL RESEARCH: BMS-MSD-Janssen- AstraZeneca-Seagen-Pfizer-Astellas-Exelixis; Non-Financial Interests, Leadership Role: Janssen-BMS; Non-Financial Interests, Personal, Product Samples: Janssen-BMS; Other, Other, ESMO MEMBER: ESMO. A.J.P.D.S. Gomes: Financial Interests, Speaker, Consultant, Advisor: Janssen; Financial Interests, Speaker’s Bureau: Astellas, Bayer, Janssen; Financial Interests, Research Funding: AstraZeneca, Bayer, Janssen, MSD, Roche. C. Helissey: Financial Interests, Speaker, Consultant, Advisor: Astellas, AstraZeneca, ACCORD, BMS, Janssen, MSD, Pfizer, Roche, Sanofi, Viatris. L.I. Karsh: Financial Interests, Speaker, Consultant, Advisor: Astellas, AstraZeneca, Aurora, Bayer, Dendreon, Ferring, Janssen, Merck, Pfizer, Sanofi, Specialty Networks/UroGPO, Vaxiion, Daiichi Sankyo. Y. Pu: Financial Interests, Personal, Advisory Board: Astellas, Ipsen, Pfizer, MSD, Roche, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Bayer. R. Ravilla: Financial Interests, Speaker’s Bureau: BMS, Exelixis, Janssen; Financial Interests, Advisory Board: Astellas/Seattle Genetics, Merck. G. Roubaud: Financial Interests, Speaker, Consultant, Advisor: Astellas, Janssen, MSD, Pfizer; Financial Interests, Research Funding: Bayer. I.A. Skoneczna: Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca, Astellas; Financial Interests, Personal, Invited Speaker: Janssen, Merck, Bayer; Financial Interests, Personal and Institutional, Local PI: Janssen, Roche, Astellas, Bayer. W. Kim, B. Espina, M. Withelder, K. Urtishak, P.S.J. Francis: Financial Interests, Full or part-time Employment: Janssen; Financial Interests, Stocks/Shares: Janssen. F. Saad: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Exelixis, Janssen, Merck, Novartis/AAA, BMS, Sanofi, Pfizer; Financial Interests, Speaker, Consultant, Advisor: Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis/AAA, Pfizer, Tolmar, Lilly, AbbVie, Myovant. All other authors have declared no conflicts of interest.