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 with diabetes were not prospectively evaluated as a subset population.^1,2
  • In the HRR+ population, hyperglycemia was reported as a treatment-emergent adverse event (TEAE) leading to treatment dose reduction at the first interim analysis.^2,3 Diabetes-related TEAEs leading to dose reduction are listed in Table: Select TEAEs Leading to Dose Reduction in the HRR+ Cohort at IA1.
  • At the second interim analysis, after a median exposure of 17.9 months in the niraparib/AAP group, hyperglycemia was reported as a TEAE in >10% of patients in the HRR+ cohort, occurring in 25 (11.8%) and 18 (8.5%) patients in the niraparib/AAP and placebo/AAP groups, respectively. Grade 3 and grade 4 hyperglycemia was reported in 6 (2.8%) and 1 (0.5%) patients in the niraparib/AAP group compared with 2 (0.9%) and 0 patients in the placebo/AAP group, respectively.⁴
• Please refer to local labeling for additional considerations.

CLINICAL DATA

MAGNITUDE Study

Chi et al (2023)^2,4,5 and Efstathiou et al (2023)⁶ 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 1000 mg PO once daily plus prednisone 5 mg twice daily.

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

MAGNITUDE Study Design^1,2,7

Abbreviations: AA, abiraterone acetate; AML, acute myeloid leukemia; AR, androgen receptor; BPI-SF, Brief Pain Inventory-Short Form; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; GnRHa, gonadotropin-releasing hormone analog; HRR, homologous recombination repair; L1, first-line therapy; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; MDS, myelodysplastic syndrome; MRI, magnetic resonance imaging; NIRA, niraparib; nmCRPC, non-metastatic castration-resistant prostate cancer; ORR, objective response rate; OS, overall survival; PARPi, poly ADP-ribose polymerase inhibitor; PBO, placebo; PFS2, progression-free survival on first subsequent therapy; PO, orally; PSA, prostate-specific antigen; R, randomization; rPFS, radiographic progression-free survival; TCC, time to cytotoxic chemotherapy; TSP, time to symptomatic progression; TTPP, time to PSA progression.
^aNovel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy; or >4 months of AAP before randomization.

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

Efficacy and Safety

• Efficacy and safety analyses were not specifically reported for patients with diabetes mellitus at baseline in the MAGNITUDE study.
• At the first interim analysis, the median total duration of assigned treatment for the HRR+ cohort was 13.8 months (range, 0-29.0) in the niraparib/AAP group and 12.1 months (range, 0-29.0) in the placebo/AAP group. In the niraparib/AAP group, hyperglycemia was reported as a TEAE leading to dose reduction of abiraterone acetate (n=1) and prednisone (n=3).³  Diabetes-related TEAEs leading to dose reduction are listed in Table: Select TEAEs Leading to Dose Reduction in the HRR+ Cohort at IA1.

• At the second interim analysis, after a median exposure of 17.9 months in the niraparib/AAP group, hyperglycemia was reported as a TEAE in >10% of patients, occurring in 25 (11.8%) and 18 (8.5%) patients in the niraparib/AAP and placebo/AAP groups, respectively. Grade 3 and grade 4 hyperglycemia were reported in 6 (2.8%) and 1 (0.5%) patients in the niraparib/AAP group compared to 2 (0.9%) and 0 patients in the placebo/AAP group, respectively.⁴

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 20 July 2024. Summarized in this response and relevant data pertaining to this topic in patients with prostate cancer.