Eleni Efstathiou, MD, PhD, discusses second interim findings from a subgroup analysis of the phase 3 MAGNITUDE trial in patients with BRCA-mutated metastatic castration-resistant prostate cancer.
Eleni Efstathiou, MD, PhD, section chief, Genitourinary Medical Oncology, Houston Methodist Oncology Partners, discusses second interim findings from a subgroup analysis of the phase 3 MAGNITUDE trial (NCT03748641) in patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).
MAGNITUDE randomized 423 patients 1:1 to receive either niraparib (Zejula) plus abiraterone acetate (Zytiga) or placebo plus abiraterone acetate. This prespecified second interim analysis included an assessment of the primary and secondary end points radiographic progression-free survival (rPFS), time to symptomatic progression, and time to cytotoxic chemotherapy in the subgroup of 225 patients with BRCA mutations.
In prostate cancer, patients with BRCA mutations comprise 1 of the most aggressive patient subgroups, Efstathiou says. Previously, retrospective data have shown that patients with BRCA-mutated disease perform poorly on the current standards of care, either chemotherapy or next-generation hormonal agents, Efstathiou notes. As a result, 1 of the main goals of MAGNITUDE was to evaluate the potential benefit of niraparib plus abiraterone acetate in this subgroup, which has many unmet needs, Efstathiou emphasizes.
At 8.1 months of additional follow-up, this subgroup analysis showed that the median rPFS in the patients with BRCA mutations who received placebo plus abiraterone acetate was 10.9 months, Efstathiou explains. These findings demonstrate poorer outcomes in patients with BRCA mutations compared with the historically observed rPFS of 16.5 months in an unselected population treated with abiraterone acetate alone in the phase 3 COU-AA-302 trial (NCT00887198), Efstathiou says.
Conversely, this second interim analysis showed a median rPFS of 19.5 months in patients with BRCA-mutated disease who received niraparib plus abiraterone acetate, which is almost double the median rPFS in the control arm, Efstathiou emphasizes. This translates to a 45% reduction in the risk of progression or death in the BRCA-mutated mCRPC population, Efstathiou notes. These data are an important development for patients with BRCA-mutated mCRPC, Efstathiou concludes.