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., 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
Abstract
There was no significant difference in time to deterioration of pain between niraparib in combination with abiraterone acetate plus prednisone (AAP) and placebo plus AAP, and overall health-related quality of life was maintained in patients with BRCA1/2 -altered metastatic castration-resistant prostate cancer. The patient-reported impact of side effects was minimal, and all side effects were clinically managed. 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 BRCA 1/2 alterations ( BRCA + ). 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. 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. 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.