The FDA has approved niraparib and abiraterone acetate to treat patients with deleterious or suspected deleterious BRCA-positive mCRPC, as detected by an FDA-approved test.
The FDA has approved the dual-action tablet (Akeega) to treat patients with deleterious or suspected deleterious BRCA-positive metastatic castration-resistant prostate cancer, as detected by an FDA-approved test. The tablet is comprised of niraparib (Zejula) and abiraterone acetate (Zytiga).
The regulatory decision is supported by findings from the phase 3 MAGNITUDE trial (NCT03748641), which demonstrated that the tablet, along with prednisone, significantly improved radiographic progression-free survival (rPFS) over abiraterone acetate plus prednisone alone in this patient population (HR, 0.53; P =.001).
Moreover, at a second interim analysis, at a follow-up of 24.8 months, patients in the BRCA-positive subgroup achieved a median rPFS of 19.5 months with the tablets vs 10.9 months with placebo and AAP (HR, 0.55; 95% CI, 0.39-0.78).
The agent was also associated with improved time to symptomatic progression (HR, 0.54; 95% CI, 0.35-0.85) and time to cytotoxic chemotherapy (HR, 0.56; 95% CI, 0.35-0.90) compared with the control regimen, with the data trending towards an overall survival improvement (HR, 0.88; 95% CI, 0.58-1.34).
"As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation," Kim Chi, MD, medical oncologist at BC Cancer – Vancouver and principal investigator of the phase 3 MAGNITUDE study, said in a news release. "We prospectively designed the MAGNITUDE study to identify the subset of patients most likely to benefit from targeted treatment with AKEEGA and to help us understand how we can potentially achieve better health outcomes for patients."
The combination demonstrated a safety profile during the trial that was consistent with the preexisting safety profiles associated with each of the agents as monotherapy. A total of 41% of patients reported a serious adverse event (AE). The most common AEs, occurring in at least 20% of patients on the trial, included musculoskeletal pain (44% vs 42%, respectively), fatigue (43% vs 30%), constipation (34% vs 20%), hypertension (33% vs 27%), and nausea (33% vs 21%).
This new approval marks the first-and-only orally administered dual action tablet consisting of a PARP inhibitor and an androgen biosynthesis inhibitor. The recommended dose is 200 mg niraparib/1,000 mg abiraterone acetate (2 tablets) daily.
Of note, the tablet comes with warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, hypokalemia, fluid retention, and cardiovascular adverse reactions, hepatotoxicity, adrenocortical insufficiency, hypoglycemia, increased fractures and mortality in combination with radium 223 dichloride, posterior reversible encephalopathy syndrome, and embryo-fetal toxicity.
"The approval of AKEEGA brings an important treatment option to patients with prostate cancer as they consider their road ahead, and it also highlights the importance of genetic testing and precision medicine for this disease," Shelby Moneer, MS, CHES, vice president of patient programs and education, ZERO Prostate Cancer, said. "All individuals diagnosed with prostate cancer should consider genetic testing, especially those from racial and ethnic minority groups who tend to have worse cancer outcomes. This is imperative to close the racial and ethnic disparities in prostate cancer health outcomes."
U.S. FDA approves AKEEGA (niraparib and abiraterone acetate), the first-and-only dual action tablet for the treatment of patients with BRCA-positive metastatic castration-resistant prostate cancer. News release. Janssen. August 11, 2023. Accessed August 11, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-akeega-niraparib-and-abiraterone-acetate-the-first-and-only-dual-action-tablet-for-the-treatment-of-patients-with-brca-positive-metastatic-castration-resistant-prostate-cancer-301899028.html