Efstathiou Discusses Impact of Niraparib Combo From MAGNITUDE in mCRPC

Eleni Efstathiou, MD, PhD, spoke about how results of the phase 3 MAGNITUDE trial, which examined the combination of niraparib with abiraterone acetate and prednisone, have the ability to change the standard of care in patients with metastatic castration-resistant prostate cancer.

In an interview with CancerNetwork® during the 2022 Genitourinary Cancer Symposium, Eleni Efstathiou, MD, PhD, section chief of Genitourinary Medical Oncology at Houston Methodist Oncology Partners in Texas, spoke about the benefits derived from niraparib (Zejula) plus abiraterone acetate and prednisone in the phase 3 MAGNITUDE trial (NCT03748641) and why these results could impact the standard of care for men with metastatic castration-resistant prostate cancer who are treated with first-line therapy.

Patients treated with the combination who harbored BRCA1/2 mutations had a reduced risk of disease progression or death of 47% (HR, 0.53; 95% CI, 0.36-0.79; P = .0014), and those with homologous recombination repair had a reduction of 27% (HR, 0.73; 95% CI, 0.56-0.96; P = .0217).


The study gave us the first signal of a positive outcome in men who harbor germline or somatic mutations and have metastatic castration-resistant prostate cancer that has failed initial medical castration. The big question is, how does this translate into everyday clinical practice? We will be eagerly anticipating the final analysis, but the radiographic progression-free survival benefit leaves no doubt that across the board for men with such mutations, there is an anticipated benefit of at least 30%. If you look specifically at that subset of men with BRCA1/2 germline [or somatic mutations, you can observe] a reduction in the risk of progression or death that is reaching almost 50%, which is impressive.

The next step will be to hear from the FDA [about] when we will have the agent approved, and more importantly, how we will introduce it in the clinic. The biggest consideration here is that many of our patients are now exposed to enhanced androgen signaling inhibition with abiraterone in the castration-naïve setting. How we will integrate [treatment] in those who have these mutations in their tumors remains to be answered.


Chi K, Rathkopf D, Smith M, et al. Phase 3 MAGNITUDE study: first results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration- resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2022; 40(suppl_6):12. doi: 10.1200/JCO.2022.40.6_suppl.012