Summary

• Hematologic adverse reactions, including thrombocytopenia, anemia, and neutropenia, have been reported in patients treated with AKEEGA. These adverse reactions generally occur early during treatment and are managed with laboratory monitoring and dose modifications.¹ Please refer to local labeling for additional considerations.
• In MAGNITUDE, the 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, hematologic events were reported as a treatment-emergent adverse event (TEAE).^2-5
  • Patients with a history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and patients who received a transfusion (platelets or red blood cells) or hematopoietic growth factors up to 28 days prior to randomization were excluded from the study.⁶
  • At the first interim analysis (IA1):
    • Hematologic TEAEs leading to dose reduction or discontinuation are included in Table: Hematologic TEAEs Leading to Dose Reduction or Discontinuation in the MAGNITUDE HRR+ Cohort at IA1.
  • At the second interim analysis (IA2)⁴:
    • No new safety signals were observed.
    • Hematologic TEAEs reported in the HRR+ cohort are described in Table: Hematologic TEAEs (Occurring in >10% of Patients) in the MAGNITUDE HRR+ Cohort at IA2.
  • At the final analysis for overall survival (OS)⁷:
    • Hematologic TEAEs reported in the HRR+ cohort are described in Table: Hematologic TEAEs of Special Interest in the MAGNITUDE HRR+ Population at the Final Analysis.
• In AMPLITUDE, the phase 3 study evaluating the efficacy and safety of AKEEGA with prednisone in patients with deleterious germline or somatic HRR gene-altered metastatic castration-sensitive prostate cancer (mCSPC; N=696), hematologic events were reported as a TEAE.⁸ 
  • Hematologic TEAEs reported at the first interim analysis in the HRR+ population are described in Table: Hematologic TEAEs in the AMPLITUDE Study at IA1.

CLINICAL DATA

MAGNITUDE Study

Chi et al (2023)^3,4 and Efstathiou et al (2023)⁹ reported the efficacy and safety of AKEEGA with prednisone compared to placebo/abiraterone acetate with prednisone (AAP) in mCRPC for patients with certain HRR mutations (n=423), including BRCA1/2 (n=225). Patients were randomized 1:1 to receive niraparib 200 mg by mouth (PO) once daily or matching placebo in combination with abiraterone acetate 1000 mg PO once daily plus prednisone 5 mg twice daily.

The study design is presented in Figure: MAGNITUDE Study Design.

• Patients were excluded if they had a history or evidence of any of the following conditions:
  • History or current diagnosis of MDS/AML.⁶
  • A transfusion (platelets or red blood cells) or hematopoietic growth factors up to 28 days prior to randomization.⁶

Hematologic Events

• The median total duration of assigned treatment for the HRR+ cohort was 13.8 months in the niraparib/AAP group and 12.1 months in the placebo/AAP group.³
• At IA1, the median follow-up was 18.6 months. Hematologic TEAEs leading to dose reduction or discontinuation are included in Table: Hematologic TEAEs Leading to Dose Reduction or Discontinuation in the MAGNITUDE HRR+ Cohort at IA1.
  • Anemia was a common grade 3 adverse event (AE; 29.7% vs 7.6%) in the niraparib/AAP vs placebo/AAP group, respectively.³ Additional grade ≥3 AEs included thrombocytopenia (6.6% vs 2.4%), neutropenia (6.6% vs 1.4%), and leukopenia (1.9% vs 0.5%) in the niraparib/AAP vs placebo/AAP group, respectively.

• The safety profile at IA2 was consistent with that of IA1, with no new safety signals observed. Hematologic TEAEs reported in the HRR+ cohort are described in Table: Hematologic TEAEs (Occurring in >10% of Patients) in the MAGNITUDE HRR+ Cohort at IA2.⁴
  • Anemia was among the most common (≥10%) grade ≥3 AEs for niraparib/AAP vs placebo/AAP reported in 30.2% vs 8.5%, respectively. Anemia was the most common cause of dose interruption or dose reduction of niraparib, followed by thrombocytopenia and neutropenia.
  • Transfusion support for anemia was required by 27.4% of patients in the niraparib/AAP group and by 5.2% of patients in the placebo/AAP group, with 16.8% and 2.5%, respectively, receiving only one transfusion.
  • There were no cases of MDS/AML in patients treated with niraparib/AAP.

• At the final analysis for OS, the median follow-up was 37.3 months. Hematologic TEAEs of special interest are summarized in Table: Hematologic TEAEs of Special Interest in the MAGNITUDE HRR+ Population at Final Analysis.⁷ Transfusion rates were 27.3% vs 5.2% in the niraparib/AAP vs placebo/AAP group, respectively.⁵

AMPLITUDE Study 

Attard et al (2025)⁸ reported the efficacy and safety of AKEEGA plus ADT compared with placebo/AAP plus ADT in patients with deleterious germline or somatic HRR gene-altered mCSPC (N=696).

The study design is presented in Figure: AMPLITUDE Study Design.

• Patient characteristics were well balanced between the 2 groups.

Hematologic Events

• A summary of hematologic events reported in both treatment arms is shown in Table: Hematologic TEAEs in the AMPLITUDE Study at IA1.

ADDITIONAL INFORMATION

Monitoring and Management

Hematologic adverse reactions have been reported in patients treated with AKEEGA.¹ These adverse reactions generally occur early during treatment and were managed with laboratory monitoring and dose modifications per protocol in the MAGNITUDE study. Please refer to local labeling for additional considerations, such as dose modifications.

In the MAGNITUDE study, patients were monitored and managed as follows¹:

• Testing complete blood counts weekly for the first month, every 2 weeks for the next 2 months, followed by monthly monitoring for the first year, and then periodically for the remainder of treatment is recommended to monitor for clinically significant changes in any hematologic parameter while on treatment.
  • Based on individual laboratory values, weekly monitoring for the second month may be warranted.
• If a patient develops severe persistent hematologic toxicity, including pancytopenia, that does not resolve within 28 days following interruption, AKEEGA should be discontinued.
• Due to the risk of thrombocytopenia, other medicinal products known to reduce platelet counts should be used with caution in patients taking AKEEGA.

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 23 May 2025. Summarized in this response are relevant data limited to the phase 3 MAGNITUDE and AMPLITUDE studies in patients with mCRPC and mCSPC, respectively.