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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

Kim N Chi1, Dana Rathkopf2, Matthew R Smith3

  • 1BC Cancer - Vancouver Center, University of British Columbia, Vancouver, BC, Canada.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|March 23, 2023
PubMed

Insights

Niraparib plus abiraterone acetate significantly improved radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer and homologous recombination repair alterations. This combination offers a new treatment option for HRR+ mCRPC.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease with limited treatment options.
  • Homologous recombination repair (HRR) gene alterations, such as BRCA1/2, can make cancer cells sensitive to poly (ADP-ribose) polymerase inhibitors.
  • Combining poly (ADP-ribose) polymerase inhibition with androgen receptor signaling inhibition may improve outcomes in treatment-naïve mCRPC.

Purpose of the Study:

  • To evaluate the efficacy and safety of niraparib plus abiraterone acetate and prednisone (niraparib + AAP) versus placebo plus AAP in patients with mCRPC.
  • To assess the impact of HRR-associated gene alterations on treatment outcomes.
  • To determine the primary endpoint of radiographic progression-free survival (rPFS) in specific patient subgroups.

Main Methods:

  • The MAGNITUDE study was a phase III, randomized, double-blinded trial (NCT03748641).
  • Patients were assigned to receive either niraparib + AAP or placebo + AAP (1:1 ratio).
  • Patients were stratified based on the presence (HRR+, n=423) or absence (HRR-, n=247) of HRR-associated gene alterations, prospectively determined by tissue/plasma assays.

Main Results:

  • In the BRCA1/2 subgroup, median rPFS was significantly longer with niraparib + AAP (16.6 months) versus placebo + AAP (10.9 months; HR, 0.53; P=.001).
  • In the overall HRR+ cohort, median rPFS was significantly longer with niraparib + AAP (16.5 months) versus placebo + AAP (13.7 months; HR, 0.73; P=.022).
  • Secondary endpoints, including time to symptomatic progression and time to chemotherapy initiation, also showed improvement. Futility was declared in the HRR- cohort. Treatment was tolerable, with anemia and hypertension as common grade ≥3 adverse events.

Conclusions:

  • Combination treatment with niraparib + AAP significantly improved rPFS in patients with HRR+ mCRPC compared to standard-of-care AAP.
  • Niraparib + AAP demonstrates a significant benefit for patients with HRR alterations in mCRPC.
  • The combination therapy is a tolerable and effective option for this patient population.

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