Summary

• MAGNITUDE is a phase 3 study evaluating the efficacy and safety of AKEEGA with prednisone as first-line (L1) therapy in metastatic castration-resistant prostate cancer (mCRPC) for patients with certain homologous recombination repair (HRR) mutations, including BRCA1/2.^1-4
  • Hemorrhage was among the most common adverse reactions (≥10%) reported in patients who received AKEEGA. In the AKEEGA with prednisone group (N=113) vs placebo with abiraterone acetate plus prednisone (AAP) group (N=112), all grades reported were 12% vs 8% and grade 3-4 reported were 2% vs 1%, respectively. Serious adverse reactions reported in >2% of patients who received AKEEGA included hemorrhage (3.5%).⁵
• QUEST was a phase 1b-2, multicenter, open-label study evaluating the safety, tolerability, and efficacy of niraparib in combination with other anti-cancer therapies, including either cetrelimab, an investigational, intravenous, monoclonal antibody against programmed cell death receptor-1 (PD-1), or AAP, for the treatment of mCRPC in patients with HRR gene alterations who progressed on prior androgen-receptor targeted (ART) therapy for prostate cancer.^6-8
  • Lower gastrointestinal (GI) hemorrhage was observed as a serious drug-related adverse event in 1/24 patients in the niraparib with AAP group.
• Hemorrhage was identified as a potential signal of a serious risk/new safety information for AKEEGA by the Adverse Event Reporting System (FAERS), per routine US Food and Drug Administration (FDA) publication. The FDA is evaluating the need for regulatory action.⁹

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 29 July 2024. Summarized in this response are relevant data pertaining to this topic in patients with prostate cancer.