{"entity":{"id":"magnitude","kind":"trial","name":"MAGNITUDE","aka":[],"tldr":"PARP inhibitor plus abiraterone helped men with BRCA mutations and did nothing for those without, settling a debate.","summary":"MAGNITUDE, trial NCT03748641 sponsored by Janssen and reported in 2022, tested adding the PARP inhibitor niraparib to abiraterone in first-line metastatic castration-resistant prostate cancer in separate cohorts with and without homologous recombination repair alterations, and it settled a debate: the combination helped men with BRCA mutations and did nothing for those without. The HRR-negative cohort was stopped for futility, while the BRCA cohort met its radiographic progression-free survival endpoint and showed a survival benefit at update, and the fixed-dose combination Akeega was approved in 2023 for BRCA-mutant disease. OnCo links it to BRCA1 and BRCA2 as targets, to niraparib and abiraterone acetate. Whether the negative HRR-negative result applies to other PARP inhibitors is the open question.","status":"mixed","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT03748641","url":"https://clinicaltrials.gov/study/NCT03748641"},{"label":"NICE TA1032: niraparib with abiraterone acetate and prednisone for untreated hormone-relapsed metastatic prostate cancer, terminated appraisal","url":"https://www.nice.org.uk/guidance/terminated/ta1032"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["parp-inhibitor"],"targets":["brca"],"drugs":["niraparib","abiraterone"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["prostate-hrr-eligibility","prostate-uk-drug-approvals"],"trials":["propel","talapro-2"],"people":["kim-chi"],"bottlenecks":[],"keyPapers":["paper-magnitude-j-clin-oncol-2023"],"journals":[],"dependsOn":[],"notes":["Niraparib with abiraterone acetate and prednisone has no NICE recommendation in England. NICE TA1032, terminated on 22 January 2025, states that NICE is unable to make a recommendation because Johnson and Johnson Innovative Medicine did not provide an evidence submission, and that the decision will be reviewed if the company submits. A terminated appraisal is not a refusal on the evidence; it is the absence of any evidence for NICE to appraise."],"nct":"NCT03748641","phase":"3","setting":"First-line mCRPC: abiraterone + niraparib vs abiraterone + placebo, HRR-mutant and HRR-negative cohorts","sponsor":"Janssen","result":"BRCA cohort rPFS HR 0.53; HRR-negative futility.","started":"2019-01-25","startedType":"actual","yearReported":2022,"enrolled":423,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 765 participants (actual) across all cohorts; the JCO 2023 primary analysis randomised 423 patients in the HRR-positive cohort, the population behind the headline result, and 247 in the HRR-negative cohort.","outcomes":[{"endpoint":"Radiographic progression-free survival, BRCA1/2 subgroup","primary":true,"unit":"months","arms":[{"name":"Niraparib + abiraterone","n":113,"value":16.6},{"name":"Placebo + abiraterone","n":112,"value":10.9}],"hr":0.53,"ci":[0.36,0.79],"p":"0.001","source":"https://ascopubs.org/doi/10.1200/JCO.22.01649"}],"replication":"Consistent with PROpel and TALAPRO-2 in BRCA-mutant disease; the HRR-negative cohort showed no benefit and was stopped for futility."},"route":"/trials/magnitude/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"term":[{"id":"data-monitoring-committee","kind":"term","name":"Data monitoring committee (DSMB, IDMC)","route":"/terms/data-monitoring-committee/"},{"id":"biomarker-stratified-design","kind":"term","name":"Enrichment and biomarker-stratified designs","route":"/terms/biomarker-stratified-design/"},{"id":"futility","kind":"term","name":"Futility analysis (stopped for futility)","route":"/terms/futility/"},{"id":"group-sequential-design","kind":"term","name":"Group sequential design, stopping rules and alpha spending","route":"/terms/group-sequential-design/"},{"id":"prespecified-vs-post-hoc","kind":"term","name":"Pre-specified vs post-hoc analysis","route":"/terms/prespecified-vs-post-hoc/"},{"id":"prostate-uk-drug-approvals","kind":"term","name":"Prostate cancer drugs in England: what NICE recommends, and what it refuses","route":"/terms/prostate-uk-drug-approvals/"},{"id":"subgroup-analysis","kind":"term","name":"Subgroup analysis (forest plots)","route":"/terms/subgroup-analysis/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"trial":[{"id":"propel","kind":"trial","name":"PROpel","route":"/trials/propel/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"},{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"}],"person":[{"id":"kim-chi","kind":"person","name":"Kim N. Chi","route":"/people/kim-chi/"}],"paper":[{"id":"paper-magnitude-j-clin-oncol-2023","kind":"paper","name":"Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer","route":"/key-papers/paper-magnitude-j-clin-oncol-2023/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}