The US Food and Drug Administration (FDA) has approved niraparib and abiraterone acetate (Akeega, Janssen Pharmaceuticals) to treat BRCA-positive, metastatic castration-resistant prostate cancer in adult patients with deleterious or suspected deleterious disease, as determined by an FDA-approved test.
The once-daily dual-action tablet is the first-and-only orally administered treatment combining the PARP inhibitor niraparib with abiraterone acetate.
The FDA’s approval was based on findings from the phase 3 MAGNITUDE precision medicine study, a randomized, placebo-controlled trial with 423 patients, 225 (53%) of whom had BRCA gene mutations as determined using a tissue assay such as FoundationOne CDx.
Among the subgroup with a BRCA mutation, radiographic progression-free survival was a median of 16.6 months vs 10.9 months (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.36 – 0.79; P = .0014). In this subgroup, an exploratory overall survival analysis demonstrated a median of 30.4 months vs 28.6 months (HR, 0.79; 95% CI, 0.55 – 1.12), favoring the treatment arm.
Although the overall cohort (those with and without BRCA mutations) demonstrated a significant improvement in radiographic progression-free survival, the subgroup with non-BRCA homologous recombination repair mutations did not demonstrate a significant improvement in radiographic progression-free survival, which indicates that the benefit observed was “primarily attributed” to the results in the subgroup of patients with BRCA mutations, according to the FDA.
The safety profile of niraparib and abiraterone acetate plus prednisone was consistent with the known safety profile of each FDA-approved monotherapy. Serious adverse events occurred in 41% of patients in the treatment arm. These most often included musculoskeletal pain (44% vs 42%), fatigue (43% vs 30%), constipation (34% vs 20%), hypertension (33% vs 27%), and nausea (33% vs 21%).
An adverse reaction led to permanent discontinuation of treatment in 15% of patients.
“As a physician, identifying patients with a worse prognosis is a priority, especially those whose cancers have a BRCA mutation,” principal investigator Kim Chi, MD, stated in the Janssen press 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.”
About 10% – 15% of patients who develop metastatic castration-resistant prostate cancer have BRCA gene alterations, and those patients are more likely to have aggressive disease, poor outcomes, and shorter survival. Therefore, this new agent “brings an important treatment option to patients with prostate cancer as they consider their road ahead,” said Shelby Moneer, vice president of patient programs and education at ZERO Prostate Cancer.
The prescribing information lists the recommended dose at 200 mg niraparib and 1000 mg abiraterone once daily in combination with 10 mg of prednisone daily until disease progression or unacceptable toxicity. Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on Twitter: @SW_MedReporter .
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