(UroToday.com) On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on prostate cancer, Dr. Elena Castro presented in Poster Session A on the effect of run-in treatment using abiraterone acetate and prednisone on the effect of combination therapy with abiraterone and niraparib for men with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations in the MAGNITUDE trial.
As has previously been reported, the combination of abiraterone and niraparib (as compared to abiraterone) significantly improved outcomes in patients with mCRPC and HRR gene alterations, particularly in BRCA, in the phase 3 MAGNITUDE study (NCT03748641). As a practical measure, patients were permitted to receive up to 4 months of abiraterone (in 1L mCRPC) prior to randomization to allow time for genomic testing. In this abstract, the authors evaluated the impact of abiraterone run-in treatment on the efficacy of abiraterone and niraparib.
In the context of MAGNITUDE, 423 patients with mCRPC and HRR gene alterations were randomized 1:1 to receive abiraterone and niraparib or placebo and abiraterone. At the prespecified second interim analysis, these authors performed a sensitivity analysis based on the duration of abiraterone run-in. Patients with BRCA alterations were also analyzed separately.
Among these 423 patients, the median duration of prior abiraterone treatment received was 1.9 (range, 0.3–4.1) months. Patients who received abiraterone for two or fewer had similar benefit (radiographic progression-free survival [rPFS] hazard ratio [HR], 0.69 [95% confidence interval [CI], 0.36-1.30]; time to cytotoxic chemotherapy [TCC] HR, 0.52 [95% CI, 0.24-1.11]; time to symptomatic progression [TSP] HR, 0.32 [95% CI, 0.13-0.79]) to patients not receiving any prior abiraterone. Importantly, rPFS benefit was not demonstrated in patients who had previously received abiraterone >2 – 4 months: HR, 1.47 (95% CI, 0.66-3.30). Findings were consistent in the BRCA population.
In this follow-up analysis of the MAGNITUDE trial, patients receiving a short run-in (≤2 months) of abiraterone alone obtained similar benefit from abiraterone and niraparib as those who received both abiraterone and niraparib together for initial treatment of mCRPC. While interpretation of data is limited by the small sample size and event numbers, for patients where abiraterone and niraparib is being considered as therapy, abiraterone may be initiated during HRR testing and combination treatment should be initiated expeditiously once HRR positivity is established to attain maximal treatment benefit.
Presented by: Elena Castro, MD, PhD, Medical Oncologist, Virgen de la Victoria University Hospital in Malaga, Spain