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

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

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

Eur Urol. 2024 Sep 23:S0302-2838(24)02594-6. doi: 10.1016/j.eururo.2024.09.003. Online ahead of print.

Authors

Dana E Rathkopf¹, Guilhem Roubaud², Kim N Chi³, Eleni Efstathiou⁴, Gerhardt Attard⁵, David Olmos⁶, Eric J Small⁷, Marniza Saad⁸, Elena Castro⁹, Won Kim¹⁰, Daphne Wu¹⁰, Kristi Bertzos¹¹, Shiva Dibaj¹², Jenny Zhang¹⁰, Peter Francis¹³, Matthew R Smith¹⁴

Affiliations

¹ Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA. Electronic address: rathkopd@mskcc.org.
² Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
³ BC Cancer, University of British Columbia, Vancouver, Canada.
⁴ Houston Methodist Cancer Center, Houston, TX, USA.
⁵ University College London, London, UK.
⁶ Department of Medical Oncology, Instituto de Investigación Sanitaria, Hospital Universitario, 12 de Octubre, Madrid, Spain.
⁷ Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA, USA.
⁸ Department of Clinical Oncology, University of Malaya, Kuala Lumpur, Malaysia.
⁹ Intercentre Clinical Management Unit for Medical Oncology, University Hospital Virgen de la Victoria, Málaga, Spain.
¹⁰ Janssen Research & Development, LLC, Los Angeles, CA, USA.
¹¹ Janssen Global Services, LLC, Horsham, PA, USA.
¹² Janssen Research & Development, LLC, San Diego, CA, USA.
¹³ Janssen Research & Development, LLC, Raritan, NJ, USA.
¹⁴ Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA.

PMID: 39317633
DOI: 10.1016/j.eururo.2024.09.003

Abstract

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.

Keywords: Abiraterone acetate plus prednisone; Brief Pain Inventory–Short Form; EQ-5D-5L; Functional Assessment of Cancer Therapy–Prostate; Health-related quality of life; Metastatic castration-resistant prostate cancer; Niraparib; Patient-reported outcomes.

Associated data

ClinicalTrials.gov/NCT03748641