Background: NIRA/AAP significantly improved outcomes in pts with mCRPC and HRR gene alterations, particularly in BRCA, in the phase 3 MAGNITUDE study. As a practical measure, pts were permitted to receive up to 4 mos of AAP (in 1L mCRPC) prior to randomization to allow time for genomic testing. We evaluated the impact of AAP run-in treatment on the efficacy of NIRA/AAP. Methods: 423 pts with mCRPC and HRR gene alterations were randomized 1:1 to receive NIRA/AAP or placebo (PBO)/AAP. At the prespecified second interim analysis, a sensitivity analysis based on the duration of AAP run-in was conducted. Pts with BRCA alterations were also analyzed separately. Results: Median duration of prior AAP treatment received was 1.9 (range, 0.3–4.1) mos. Pts receiving AAP ≤2 mos 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]; Table) to pts not receiving any prior AAP. rPFS benefit was not demonstrated in pts who had previously received AAP >2 – 4 mos: HR, 1.47 (95% CI, 0.66-3.30). Findings were consistent in the BRCA population. Conclusions: Pts receiving a short run-in (≤2 mos) of AAP alone obtained similar benefit from NIRA/AAP as those who received both NIRA/AAP together for initial treatment of mCRPC. While interpretation of data is limited by the small sample size and event numbers, for pts where NIRA/AAP is being considered as therapy, AAP may be initiated during HRR testing and combination treatment should be initiated expeditiously once HRR positivity is established to attain maximal treatment benefit. Clinical trial information: NCT03748641.

NE, not evaluable.