KEY TAKEAWAYS
- The phase 3 MAGNITUDE study evaluated the impact of AAP on the effectiveness of NIRA+AAP treatment for mCRPC and HRR gene alterations.
- A sensitivity analysis was conducted for all patients with HRR gene alterations and those specifically with BRCA alterations.
- The study suggested that initiating AAP during HRR testing and subsequently accelerating the NIRA+AAP combination therapy upon confirmation of HRR positivity could lead to the most substantial treatment benefits.
The phase 3 MAGNITUDE study demonstrated that the combination of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) had a remarkable impact on clinical outcomes for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC), possessing alterations in homologous recombination repair (HRR) genes, particularly with BRCA. Before randomization, pts received up to 4 months of AAP as an initial mCRPC treatment, allowing time for genomic testing.
During the predetermined second interim analysis, a sensitivity analysis was carried out for pts (N=423) with mCRPC and HRR gene alterations, randomized in a 1:1 ratio to receive either NIRA+AAP or placebo/AAP. A different analysis was performed for pts (N=225) with BRCA alterations. The outcomes are hazard ratios (HR) and corresponding 95% confidence intervals (CI).
Among the pts (n=98) who received prior AAP treatment, the median duration was 1.9 mo(range-0.3 to 4.1). The advantages of treatment were comparable in pts who underwent a run-in treatment with AAP ≤2 mos before starting NIRA. The similarity was observed in terms of radiographic progression-free survival (rPFS; hazard ratio [HR], 0.69 [95% confidence interval [CI], 0.36-1.30]), time to cytotoxic chemotherapy (TCC; 0.52 [0.24-1.11]), and time to symptomatic progression (TSP; 0.32 [0.13-0.79]) compared to pts who had not previously received. However, no advantage was seen in rPFS for pts who received AAP treatment for more than 2 to 4 mos (1.47 [0.66-3.30]). These findings were consistent among the BRCA population.
The advantages of NIRA+AAP treatment were noted in pts who underwent a brief run-in period (<2 mos) of AAP, compared to those who received the combined NIRA+AAP treatment as an initial approach for mCRPC. These findings imply that the commencement of AAP during HRR testing and subsequent acceleration of NIRA+AAP combination therapy upon confirmation of HRR positivity could lead to the most substantial treatment benefits.
Source: https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/13536
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03748641
Smith, M., Efstathiou, E., Rathkopf, D.E., Guckert, M., Chi, K.N.
