Dana E. Rathkopf , Guilhem Roubaud , Kim N. Chi , Eleni Efstathiou , Gerhardt Attard , David Olmos , Eric J. Small , Marniza Saad , Elena Castro , Won Kim , Daphne Wu , Kristi Bertzos , Shiva Dibaj , Jenny Zhang , Peter Francis , Matthew R. Smith
{"title":"转移性抗阉割前列腺癌和 BRCA1/2 基因改变患者的患者报告结果：随机 3 期 MAGNITUDE 试验的最终分析。","authors":"Dana E. Rathkopf , Guilhem Roubaud , Kim N. Chi , Eleni Efstathiou , Gerhardt Attard , David Olmos , Eric J. Small , Marniza Saad , Elena Castro , Won Kim , Daphne Wu , Kristi Bertzos , Shiva Dibaj , Jenny Zhang , Peter Francis , Matthew R. Smith","doi":"10.1016/j.eururo.2024.09.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and objective</h3><div>The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR<sup>+</sup> cohort with a focus on <em>BRCA</em>1/2 alterations (<em>BRCA</em><sup>+</sup>).</div></div><div><h3>Methods</h3><div>Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory–Short Form (BPI-SF), Functional Assessment of Cancer Therapy–Prostate (FACT-P), and EQ-5D-5L questionnaires. Evaluations were completed on day 1 of designated treatment cycles and during follow-up.</div></div><div><h3>Key findings and limitations</h3><div>All patients with <em>BRCA<sup>+</sup></em> mCRPC (<em>n</em> = 225) were included in the PRO analyses with average on-treatment PRO compliance >80% when completed on-site. Time to deterioration in pain according to BPI-SF and FACT-P scores did not significantly differ between niraparib + AAP and placebo + AAP. During treatment, EQ-5D-5L revealed no clinically meaningful differences in overall HRQoL between treatment arms in the <em>BRCA</em>+ subgroup. Finally, tolerability was similar between arms; side effect bother rated as “not at all” or “a little bit” ranged from 79.8% to 95.9% during treatment. Limitations include a sample size that may not have been powered to detect a difference in PROs.</div></div><div><h3>Conclusions and clinical implications</h3><div>Treatment with niraparib + AAP maintained HRQoL with minimal side-effect bother reported by most patients with <em>BRCA<sup>+</sup></em> mCRPC. Differences between treatment groups in time to pain deterioration did not meet conventional levels of statistical significance.</div><div><br>The MAGNITUDE trial is registered on ClinicalTrials.gov as NCT03748641.</div></div>","PeriodicalId":12223,"journal":{"name":"European urology","volume":"88 4","pages":"Pages 359-369"},"PeriodicalIF":25.2000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Patient-reported Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1/2 Gene Alterations: Final Analysis from the Randomized Phase 3 MAGNITUDE Trial\",\"authors\":\"Dana E. Rathkopf , Guilhem Roubaud , Kim N. Chi , Eleni Efstathiou , Gerhardt Attard , David Olmos , Eric J. Small , Marniza Saad , Elena Castro , Won Kim , Daphne Wu , Kristi Bertzos , Shiva Dibaj , Jenny Zhang , Peter Francis , Matthew R. Smith\",\"doi\":\"10.1016/j.eururo.2024.09.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and objective</h3><div>The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR<sup>+</sup> cohort with a focus on <em>BRCA</em>1/2 alterations (<em>BRCA</em><sup>+</sup>).</div></div><div><h3>Methods</h3><div>Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory–Short Form (BPI-SF), Functional Assessment of Cancer Therapy–Prostate (FACT-P), and EQ-5D-5L questionnaires. Evaluations were completed on day 1 of designated treatment cycles and during follow-up.</div></div><div><h3>Key findings and limitations</h3><div>All patients with <em>BRCA<sup>+</sup></em> mCRPC (<em>n</em> = 225) were included in the PRO analyses with average on-treatment PRO compliance >80% when completed on-site. Time to deterioration in pain according to BPI-SF and FACT-P scores did not significantly differ between niraparib + AAP and placebo + AAP. During treatment, EQ-5D-5L revealed no clinically meaningful differences in overall HRQoL between treatment arms in the <em>BRCA</em>+ subgroup. Finally, tolerability was similar between arms; side effect bother rated as “not at all” or “a little bit” ranged from 79.8% to 95.9% during treatment. Limitations include a sample size that may not have been powered to detect a difference in PROs.</div></div><div><h3>Conclusions and clinical implications</h3><div>Treatment with niraparib + AAP maintained HRQoL with minimal side-effect bother reported by most patients with <em>BRCA<sup>+</sup></em> mCRPC. Differences between treatment groups in time to pain deterioration did not meet conventional levels of statistical significance.</div><div><br>The MAGNITUDE trial is registered on ClinicalTrials.gov as NCT03748641.</div></div>\",\"PeriodicalId\":12223,\"journal\":{\"name\":\"European urology\",\"volume\":\"88 4\",\"pages\":\"Pages 359-369\"},\"PeriodicalIF\":25.2000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European urology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0302283824025946\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European urology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0302283824025946","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Patient-reported Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1/2 Gene Alterations: Final Analysis from the Randomized Phase 3 MAGNITUDE Trial
Background and objective
The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR+ cohort with a focus on BRCA1/2 alterations (BRCA+).
Methods
Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory–Short Form (BPI-SF), Functional Assessment of Cancer Therapy–Prostate (FACT-P), and EQ-5D-5L questionnaires. Evaluations were completed on day 1 of designated treatment cycles and during follow-up.
Key findings and limitations
All patients with BRCA+ mCRPC (n = 225) were included in the PRO analyses with average on-treatment PRO compliance >80% when completed on-site. Time to deterioration in pain according to BPI-SF and FACT-P scores did not significantly differ between niraparib + AAP and placebo + AAP. During treatment, EQ-5D-5L revealed no clinically meaningful differences in overall HRQoL between treatment arms in the BRCA+ subgroup. Finally, tolerability was similar between arms; side effect bother rated as “not at all” or “a little bit” ranged from 79.8% to 95.9% during treatment. Limitations include a sample size that may not have been powered to detect a difference in PROs.
Conclusions and clinical implications
Treatment with niraparib + AAP maintained HRQoL with minimal side-effect bother reported by most patients with BRCA+ mCRPC. Differences between treatment groups in time to pain deterioration did not meet conventional levels of statistical significance.
The MAGNITUDE trial is registered on ClinicalTrials.gov as NCT03748641.
期刊介绍：
European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.
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