September 27, 2023

The US Meals and Drug Administration (FDA) has permitted niraparib and abiraterone acetate (Akeega, Janssen Prescription drugs) to deal with BRCA-positive, metastatic castration-resistant prostate cancer in grownup sufferers with deleterious or suspected deleterious illness, as decided by an FDA-approved check.

The once-daily dual-action pill is the first-and-only orally administered therapy combining the PARP inhibitor niraparib with abiraterone acetate.

The FDA’s approval was primarily based on findings from the phase 3 MAGNITUDE precision medicine study, a randomized, placebo-controlled trial with 423 sufferers, 225 (53%) of whom had BRCA gene mutations as decided utilizing a tissue assay akin to FoundationOne CDx.

Among the many 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). On this subgroup, an exploratory total survival evaluation demonstrated a median of 30.4 months vs 28.6 months (HR, 0.79; 95% CI, 0.55 – 1.12), favoring the therapy arm.

Though the general cohort (these with and with out BRCA mutations) demonstrated a major enchancment in radiographic progression-free survival, the subgroup with non-BRCA homologous recombination restore mutations didn’t show a major enchancment in radiographic progression-free survival, which signifies that the profit noticed was “primarily attributed” to the ends in the subgroup of sufferers with BRCA mutations, according to the FDA.

The security profile of niraparib and abiraterone acetate plus prednisone was per the identified security profile of every FDA-approved monotherapy. Severe adversarial occasions occurred in 41% of sufferers within the therapy arm. These most frequently included musculoskeletal ache (44% vs 42%), fatigue (43% vs 30%), constipation (34% vs 20%), hypertension (33% vs 27%), and nausea (33% vs 21%).

An adversarial response led to everlasting discontinuation of therapy in 15% of sufferers.

“As a doctor, figuring out sufferers with a worse prognosis is a precedence, particularly these whose cancers have a BRCA mutation,” principal investigator Kim Chi, MD, said within the Janssen press release. “We prospectively designed the MAGNITUDE examine to establish the subset of sufferers most probably to learn from focused therapy with AKEEGA and to assist us perceive how we will doubtlessly obtain higher well being outcomes for sufferers.”

About 10% – 15% of sufferers who develop metastatic castration-resistant prostate most cancers have BRCA gene alterations, and people sufferers usually tend to have aggressive illness, poor outcomes, and shorter survival. Subsequently, this new agent “brings an vital therapy choice to sufferers with prostate most cancers as they think about their street forward,” said Shelby Moneer, vice chairman of affected person packages and training at ZERO Prostate Most cancers.

The prescribing information lists the advisable dose at 200 mg niraparib and 1000 mg abiraterone as soon as every day together with 10 mg of prednisone every day till illness development or unacceptable toxicity. Sufferers also needs to obtain a gonadotropin-releasing hormone analog concurrently or ought to have had bilateral orchiectomy.

Healthcare professionals ought to report all severe adversarial occasions suspected to be related to using any drugs and system to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

Sharon Worcester, MA, is an award-winning medical journalist primarily based in Birmingham, Alabama, writing for Medscape, MDedge, and different affiliate websites. She presently covers oncology, however she has additionally written on quite a lot of different medical specialties and healthcare subjects. She will be reached at  [email protected]  or on Twitter:  @SW_MedReporter .

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