(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Prostate, Testicular, and Penile cancers on Monday afternoon included a presentation from Dr. Dana E. Rathkopf discussing health-related quality of life (HRQoL) outcomes among patients treated with niraparib and abiraterone in men with previously untreated metastatic castration-resistant prostate cancer (mCRPC) treated in the MAGNITUDE trial.
Treatment approaches in mCRPC have evolved substantially over the past decades, beginning with the introduction of docetaxel and transformed with subsequent data from trials of novel hormonal agents including abiraterone and enzalutamide. More recently, the PROfound trial demonstrated a benefit of the PARP inhibitor olaparib in patients with previously treated mCRPC. As a result, trials of combination therapy have been undertaken. One of the first of these is MAGNITUDE (NCT03748641), a double-blind, phase III trial of abiraterone and niraparib vs abiraterone + placebo as first-line treatment in patients with mCRPC and HRR alterations (9-gene panel) which demonstrated improved radiographic progression-free survival, time to cytotoxic chemotherapy, and time to symptomatic progression, with manageable toxicity. In this study, the authors assessed HRQoL and pain among patients treated in MAGNITUDE
While previously presented at ASCO-GU 2022, the MAGNITUDE trial included patients with mCRPC and HRR alterations who ECOG status ≤1 and a Brief Pain Inventory–Short Form (BPI-SF) worst pain score ≤3 in prescreening. After enrollment, patients were randomized 1:1 to NIRA + AAP or placebo + AAP orally daily in 28-day cycles. In addition to primary oncologic endpoint assessment, HRQoL assessments were performed on day 1 of specified cycles including Functional Assessment of Cancer Therapy–Prostate (FACT-P) and BPI-SF. Changes from baseline were compared between treatment arms using repeated measures analysis. Proportional hazards regression models were used to compare time to deterioration (TTD) in worst pain intensity between arms.
Overall, completion of the HRQoL and pain measures was high (>80%) for both FACT-P and BPI-SF. When assessed longitudinally, most patients maintained low pain levels over time. Repeated measures analyses showed no clinically meaningful differences in pain over time or between arms. 
The median TTD in pain intensity was not reached in either arm. At the 25th percentile, there was a trend toward longer TTD in pain intensity with niraparib + abiraterone, as compared to placebo + abiraterone (11.1 vs 10.1 mo; HR, 0.87; 95% CI, 0.61-1.24).
Further, HRQoL was maintained with niraparib + abiraterone, with no clinically meaningful differences in FACT-P total score over time or between arms.
There was a trend toward greater worsening in early cycles on FACT-P physical wellbeing with niraparib + abiraterone, compared to placebo + abiraterone, driven by events within the known safety profile of niraparib + abiraterone (worsening of side effects bother, lack of energy, and nausea). Notably, however, overall, most patients reported minimal side effect burden.
The authors therefore conclude that, within the MAGNITUDE trial, most patients receiving first-lien treatment for mCRPC maintained low pain levels and positive HRQoL over time, with no clinically meaningful differences between treatment arms. Overall, the side effect burden was perceived as low in both arms though more patients treated with niraparib + abiraterone reported worsening side effects.
Presented by: Dana E. Rathkopf, MD, Medical Oncologist, Associate Chair, Junior Faculty Development, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY