A plain language summary of the results from the MAGNITUDE study assessing how effective and how safe niraparib and abiraterone acetate with prednisone is in patients with metastatic castration-resistant prostate cancer

Plain Language SummaryWhat is this summary about?This is a summary of the MAGNITUDE clinical study that was published in the Journal of Clinical Oncology (March 2023) and in Annals of Oncology (September 2023).Researchers looked at the combination of niraparib and abiraterone acetate with prednisone as a first treatment for adult patients with metastatic castration-resistant prostate cancer.Researchers wanted to know how effective and safe niraparib + abiraterone acetate with prednisone is in patients whose cancers had certain gene changes. Researchers focused on genes related to homologous recombination repair (HRR), a normal process that repairs damaged DNA.The best understood HRR genes are BRCA1 and BRCA2 (which code for BReast CAncer susceptibility 1 and 2 proteins) that are changed in 3–13% of patients with metastatic castration-resistant prostate cancer. We refer to these genes as BRCA1/2.Compared with cancers that lack these changes, cancers with changes in HRR genes (HRR+) may not respond as well to treatments that are normally used for metastatic castration-resistant prostate cancer, such as abiraterone acetate with prednisone.What were the main conclusions reported by the researchers?Patients who had BRCA1/2 changes had a longer time (16.6 months) before their cancer worsened compared with those who did not (10.9 months).Patients with HRR+ metastatic castration-resistant prostate cancer taking niraparib + abiraterone acetate with prednisone had a longer time (16.5 months) before their cancer worsened (tumor increased in size, cancer spread, or death) compared with those taking placebo + abiraterone acetate with prednisone (13.7 months).Patients taking niraparib + abiraterone acetate with prednisone had more side effects (99.1%) than those taking placebo + abiraterone acetate with prednisone (94.3%).These were well-known side effects of these medicines and generally managed by pausing treatment or lowering the dose.What are the key takeaways?Patients with HRR+ metastatic castration-resistant prostate cancer, especially those with BRCA1/2 changes, have better outcomes with niraparib + abiraterone acetate with prednisone compared with placebo + abiraterone acetate with prednisone.These results show the importance of testing for HRR gene changes to select treatments that are most likely to lead to improved outcomes for these patients.This is an abstract of the Plain Language Summary of Publication article.View the full Plain Language Summary PDF of this article to read the full-textThis article is related to: AcknowledgementsThe authors would like to thank the reviewers of the article for the important feedback they provided in the development of this plain language summary publication.Disclosure statementK.N. Chi reported personal fees (invited speaker) from Astellas, AstraZeneca, Janssen, Point Biopharma, and Roche; personal fees (advisory board) from AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, and BMS; personal fees (steering committee member) from AstraZeneca, Janssen, Novartis, and Roche; serving as trial chair (institutional) for AstraZeneca, Arvinas, Janssen, and Novartis; and serving as local Primary Investigator (institutional) for Arvinas.D. Rathkopf reported financial interests (trial chair) in Janssen; financial interests (steering committee member) in Janssen and Genentech; institutional research grant and clinical trial grant from Genentech; non-financial interests (advisory role) in Janssen, Genentech, AstraZeneca, Myovant, Bayer, and BMS; and non-financial interests (principal investigator) in Janssen, Genentech, Promontory, and Celgene/BMS.M.R. Smith reported personal fees (speaker, consultant, advisor) from Amgen, Astellas Pharma, Bayer, Eli Lilly and Company, Janssen Biotech, Pfizer, and Novartis and institutional research funding from Janssen Oncology, Bayer, Eli Lilly, ESSA, and Oric Pharmaceuticals.E. Efstathiou reported personal fees (speaker, consultant, advisor) from Janssen, Sanofi, Takeda, Bayer, Merck, Pfizer, Myovant, AstraZeneca, Astellas, and Tokai Pharmaceuticals and institutional research funding from Janssen-Cilag.G. Attard reported personal fees (invited speaker) from Janssen, Astellas, and AstraZeneca; personal fees (advisory board) from Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, and Novartis; royalties and being included in list of rewards to discoverers of abiraterone from the Institute of Cancer Research; fees paid to institution (advisory board) from Artera and Veracyte; institutional research grants from Janssen, Astellas, and Novartis; fees paid to institution (coordinating PI) from Janssen; fees paid to institution (local PI) from Novartis and Pfizer; non-financial interests (principal investigator) in Janssen and Astellas; nonfinancial interests (advisory role) in Janssen and AstraZeneca; and non-financial interests (project lead) in Artera and Veracyte.D. Olmos reported personal financially compensated role with Janssen and Bayer; fees paid to institution (speaker, consultant, advisor) from Janssen, AstraZeneca, and Bayer; personal fees (speaker, consultant, advisor) from Clovis Oncology, Daiichi Sankyo, MSD Oncology, and Pfizer; personal travel, accommodations, and expenses from Bayer, Janssen, Ipsen, Roche, and AstraZeneca Spain.E.J. Small reported owning stocks/shares in Fortis, Harpoon, and Teon; and personal fees (speaker, consultant, advisor) from Johnson & Johnson; personal fees (advisory board) from Janssen, Fortis.A.J.P.D.S. Gomes reported personal fees (invited speaker) from Astellas, Bayer, Janssen, and AstraZeneca and personal fees (advisory board) from Bayer and Janssen.G. Roubaud reported personal fees (advisory board) from Janssen, Astellas, and Bayer; fees paid to institution (advisory board) from Pfizer and AstraZeneca; fees paid to institution from Novartis; fees paid to institution (coordinating PI) from Bayer.M. Saad reported personal fees (invited speaker) from Johnson & Johnson, MSD, Ipsen, Eisai, Amgen, and Pfizer; personal fees (advisory board) from Johnson & Johnson, MSD, Ipsen, Eisai, Merck, and AstraZeneca; personal fees (writing engagement) from Johnson & Johnson and Ipsen; personal and institutional financial interests (local PI) in Johnson & Johnson and MSD; and non-financial interests (advisory role) in Johnson & Johnson and Amgen.S. Sandhu reported paid advisory board roles with BMS, MSD, AstraZeneca, Novartis, and Merck Serono (funds go to a research fund at Peter MacCallum Cancer Centre); institutional research grants for an investigator-initiated trial from Novartis, Genentech, Amgen, AstraZeneca, Merck Serono, MSD, and Pfizer; non-financial interests (principal investigator) in Janssen, Novartis, Genentech, BMS, and AstraZeneca; non-financial interests (independent safety and data monitoring committee) in Novartis; non-financial interests (steering committee member) in Janssen, AstraZeneca, Genentech, and BMS.A. Lopez-Gitlitz, D. Wu and P. Francis reported employment with and owning stocks/shares in Janssen.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.The authors would like to acknowledge Aryan Stanley, PhD and Jessie Arries, PhD of Ashfield Medical Communications for medical writing support funded by Janssen US Medical Affairs in accordance with Good Publications Practice 2022 guidelines (https://www.acpjournals.org/doi/10.7326/M22-1460)Patient reviewers on this PLSP have received honorarium from Future Oncology or their review work but have no other relevant financial relationships to disclose.FundingFunding information: This study was funded by Janssen Research & Development, LLC.