Summary

• 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, patients were permitted to receive prior taxane-based chemotherapy in the metastatic castration-sensitive prostate cancer (mCSPC) setting prior to randomization.^1-5 Patients were subsequently stratified by past taxane-based chemotherapy exposure.
  • A total of 113 patients with BRCA-mutated mCRPC were enrolled to receive niraparib/abiraterone acetate with prednisone (AAP), of which 26 (23.0%) patients received prior taxane-based chemotherapy for mCSPC.⁴
  • A subgroup forest plot analysis of rPFS, for the BRCA1/2 subgroup, demonstrated similar results between treatment arms for patients with a history of prior taxane-based chemotherapy (HR, 0.98; 95% CI, 0.48-2.02).⁶
  • Safety analyses were not specifically reported for patients who received prior taxane-based chemotherapy in the MAGNITUDE study.
  • A summary of treatment-emergent adverse events (TEAEs) is described in Table: Summary of Most Common (≥10% in Either Group) TEAEs. Grade ≥3 adverse events (AEs) were reported in 153 (72.2%) and 104 (49.3%) patients in the niraparib/AAP and in the placebo/AAP group, respectively. Discontinuation of niraparib or placebo due to a TEAE occurred in 15.1% of patients in the niraparib/AAP group and 5.7% of patients in the placebo/AAP group.⁴ Safety profiles at the final analysis⁵ and second interim analysis³ were consistent with that of the first interim analysis, with no new safety signals observed.

CLINICAL DATA

MAGNITUDE Study

Chi et al (2023)^2,4 and Efstathiou et al (2023)³ reported the efficacy and safety of AKEEGA with prednisone compared to placebo/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 with prednisone 5 mg twice daily. Patients were permitted to receive prior taxane-based chemotherapy in the mCSPC setting prior to randomization, and subsequently stratified by past taxane-based chemotherapy exposure. Patients who received prior taxane-based chemotherapy for mCRPC were excluded.⁷

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

Results

Patient Characteristics

• Baseline characteristics were broadly comparable between treatment arms; however, rates of visceral metastases, bone metastases, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 were imbalanced to the disadvantage of the niraparib/AAP group.²
• Prior taxane-based chemotherapy in the MAGNITUDE study is shown in Table: Prior Taxane-Based Chemotherapy in the MAGNITUDE Study (BRCA1/2 Subgroup).
  • A total of 113 patients with BRCA-mutated mCRPC were enrolled to receive niraparib/AAP, of which 26 (23.0%) patients received prior taxane-based chemotherapy for mCSPC.⁴

Efficacy

• A subgroup forest plot analysis of rPFS, for the BRCA1/2 subgroup, demonstrated similar results between treatment arms for patients with a history of prior taxane-based chemotherapy (HR, 0.98; 95% CI, 0.48-2.02).⁶

Safety

• Safety analyses were not specifically reported for patients who received prior taxane-based chemotherapy in the MAGNITUDE study.
• At the second interim analysis, a total of 211 patients in the niraparib/AAP group and 203 patients in the placebo/AAP group reported AEs, described in Table: Summary of Most Common (≥10% in Either Group) TEAEs.⁴
• Safety profiles across the first interim analysis, second interim analysis⁴, and the final analysis⁵ were consistent, with no new safety signals.

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 24 July 2024. Summarized in this response are relevant data limited to the phase 3 MAGNITUDE study in patients with mCRPC.