LBA85 - 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

Background

In the phase 3 MAGNITUDE study (NCT03748641), NIRA + AAP significantly improved radiographic progression-free survival in BRCA-mutant (BRCA+) pts. Here we present the FA of MAGNITUDE, a phase 3 study with the largest population of 1L BRCA+ mCRPC pts, reporting mature overall survival (OS) data and prespecified multivariate analysis (MVA) for OS, addressing baseline imbalances.

Methods

Eligible pts (N = 423) with HRR+ mCRPC were randomized 1:1 to NIRA + AAP (n = 212) or placebo (PBO) + AAP (n = 211) as 1L therapy. At this FA, secondary endpoints of OS and time to cytotoxic chemotherapy (TCC) were formally assessed. Updates to time to symptomatic progression (TSP) and patient-reported outcomes (PROs) in BRCA+ pts and to safety for all HRR+ pts are also reported.

Results

At FA, 225 BRCA+ pts were evaluated; 113 pts received NIRA + AAP. Median follow-up was 35.9 months. In the NIRA + AAP and PBO + AAP arms, 70% and 86% of pts received subsequent life-prolonging therapy. OS favored NIRA + AAP over PBO + AAP (Table). A prespecified MVA adjusting for baseline imbalances showed an OS benefit favoring NIRA + AAP. Continued improvement in TSP and a clinically meaningful improvement in TCC were observed with NIRA + AAP. Time to worst pain progression and time to pain interference progression also favored NIRA + AAP. No new safety signals were observed with additional treatment exposure. Pulmonary embolism occurred in 4.7% and 1.4% of pts in NIRA + AAP and PBO + AAP arms, with no cases of myelodysplastic syndrome or acute myeloid leukemia in the NIRA + AAP arm. Table: LBA85

Endpoints at FA in pts withBRCA+ mCRPC, NIRA + AAP vs PBO + AAP

Conclusions

OS favored NIRA + AAP for pts with BRCA+ mCRPC. NIRA + AAP led to improvements in TSP, TCC, and PROs. The positive benefit-risk profile supports 1L NIRA + AAP as a new standard of care for pts with BRCA+ mCRPC.

Clinical trial identification

NCT03748641.

Editorial acknowledgement

Brittany Carson, PhD, MEDiSTRAVA.

Legal entity responsible for the study

Janssen Research & Development, LLC.

Funding

Janssen Research & Development, LLC.

Disclosure

K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. E. Castro: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Janssen, MSD, Bayer, Pfizer, Daiichi Sankyo, Lilly, Medscape, Novartis; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Clovis, Pfizer, Medscaoe; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Janssen, Bayer, Pfizer; Financial Interests, Institutional, Local PI: Janssen, Pfizer, MSD. G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, Novartis; Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research; Financial Interests, Institutional, Advisory Board: Artera, Veracyte; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Novartis; Financial Interests, Institutional, Coordinating PI: Janssen; Financial Interests, Institutional, Local PI: Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Advisory Role: Janssen, AstraZeneca; Non-Financial Interests, Project Lead: Artera, Veracyte. M.R. Smith: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Astellas Pharma, Bayer, Eli Lilly and Company, Janssen Biotech, Pfizer, Novartis; Financial Interests, Institutional, Research Funding: Janssen Oncology, Bayer, Lilly, ESSA, Oric Pharmaceuticals. 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.: Bristol Myer Squib; 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 dont 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 Bristol Myer Squibb sponsored studies and don't receive any renumeration for this.: Bristol Myer Squibb; 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 Priincipal 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 Bristol Myer Squibb sponsored trial and I do not receive renumeration for this.: Bristol Myer Squibb. E. Efstathiou: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Sanofi, Takeda, Bayer, Merck, Pfizer, Myovant, AstraZeneca, Astellas, Tokai Pharmaceuticals; Financial Interests, Institutional, Research Funding: Janssen-Cilag. G. Roubaud: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer; Financial Interests, Institutional, Advisory Board: Pfizer, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Coordinating PI: Bayer. E.J.J. Small: Financial Interests, Personal, Stocks/Shares: Fortis, Harpoon, Teon; Financial Interests, Personal, Speaker, Consultant, Advisor: J&J; Financial Interests, Personal, Advisory Board: Janssen, Fortis. A.J.P.D.S. Gomes: Financial Interests, Personal, Invited Speaker: Astellas, Bayer, Janssen, AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer, Janssen. D. Rathkopf: Financial Interests, Trial Chair: Janssen; Financial Interests, Steering Committee Member: Janssen, Genentech; Financial Interests, Institutional, Research Grant, Clinical Trial Grant: Genentech; Non-Financial Interests, Advisory Role: Janssen, Genentech, AstraZeneca, Myovant, Bayer, BMS; Non-Financial Interests, Principal Investigator: Janssen, Genentech, Promontory, Celgene/BMS. M. Saad: Financial Interests, Personal, Invited Speaker: Johnson&Johnson, MSD, Ipsen, Eisai, Amgen, Pfizer; Financial Interests, Personal, Advisory Board: Johnson&Johnson, MSD, Ipsen, Eisai, Merck, AstraZeneca; Financial Interests, Personal, Writing Engagement: Johson&Johnson, Ipsen; Financial Interests, Personal and Institutional, Local PI: Johson&Johnson, MSD; Non-Financial Interests, Advisory Role: Johnson&Johnson, Amgen. H.P. Gurney: Financial Interests, Personal, Advisory Board: Merck, Pfizer, AstraZeneca, BMS, MSD, Ipsen, Astellas. G.E. Mason: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. S. Dibaj: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. D. Wu: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. B. Diorio: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. A. Lopez-Gitlitz: Financial Interests, Personal, Full or part-time Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. W. Kim: Financial Interests, Personal, Full or part-time Employment: Janssen. D. Olmos: Financial Interests, Personal, Financially compensated role: Janssen, Bayer; Financial Interests, Institutional, Financially compensated role: Astellas Pharma; Financial Interests, Institutional, Speaker, Consultant, Advisor: Janssen, AstraZeneca, Bayer; Financial Interests, Personal, Speaker, Consultant, Advisor: Clovis Oncology, Daiichi Sankyo, MSD Oncology; Financial Interests, Personal, Other, Travel, accommodations, expenses: Bayer, Janssen, Ipsen, Astellas Pharma, Roche, AstraZeneca Spain. All other authors have declared no conflicts of interest.