AKEEGA®
(niraparib and abiraterone acetate)
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AKEEGA® (niraparib and abiraterone acetate)
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AKEEGA - Effect on Prostate-Specific Antigen (PSA) Levels
Last Updated: 06/26/2024
SUMMARY
In MAGNITUDE, the ongoing, 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, progression or change in PSA level was not used as a lone indicator for disease progression or treatment discontinuation. For patients who had an increasing PSA in the absence of radiographic or clinical progression, study treatment was continued.1 - 3 - Patients who received abiraterone acetate plus prednisone (AAP) for mCRPC prior to study entry underwent prostate-specific antigen (PSA) testing to document a lack of PSA progression before random assignment.3
- Patients were prospectively allocated to cohort 1 or 2 based on prescreening for HRR biomarker positive (BM+) or biomarker negative (BM-) status, respectively, and subsequently randomized to receive niraparib or matching placebo in combination with AAP.3
- Time to PSA progression and PSA response rate were prespecified exploratory endpoints.4
, 5 These endpoints were not adjusted for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established. - At the first interim analysis, after a median follow-up of 16.7 months, prolonged median time to PSA progression was observed in the niraparib/AAP group compared to the placebo/AAP group among HRR BM+ patients (HR, 0.57; 95% CI, 0.43-0.76; nominal P<0.001).3
- In the BRCA1/2 subgroup, at the second interim analysis, median time to PSA progression doubled in the niraparib/AAP group (18.4 months) vs placebo/AAP group (9.2 months) (HR, 0.48; 95% CI, 0.33-0.70; nominal P<0.0001).5
- The objective response rate (ORR) in the BRCA1/2 subgroup was 50.0% for niraparib/AAP vs 31.3% for placebo/AAP, yielding a relative risk (RR) for response of 1.60 (95% CI, 0.98-2.62; nominal P=0.053) and a relative risk for PSA response of 1.21 (95% CI, 1.02-1.43; nominal P=0.023).5
- Results are listed in Table: Median Time to PSA Progression in the MAGNITUDE Study.
Chi et al (2023)3,5 and Efstathiou et al (2023)6
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.3
- Baseline PSA levels in the MAGNITUDE study are shown in Table: Baseline PSA Levels in the MAGNITUDE Study.
| BRCA1/2 Subgroup | HRR+ Cohort | |||
|---|---|---|---|---|
| NIRA/AAP (n=113) | PBO/AAP (n=112) | NIRA/AAP (n=212) | PBO/AAP (n=211) | |
| Median PSA at baseline, µg/L (range) | 18.7 (0.1-2225.8) | 14.1 (0.1-4400.0) | 21.4 (0-4826.5) | 17.4 (0.1-4400.0) |
| Abbreviations: AAP, abiraterone acetate with prednisone; HRR, homologous recombination repair; NIRA, niraparib; PBO, placebo; PSA, prostate-specific antigen. | ||||
Efficacy
- Results are listed in Table: Median Time to PSA Progression in the MAGNITUDE Study. These endpoints were not adjusted for multiple comparisons. Therefore, the P-value is nominal and statistical significance has not been established.
- At the first interim analysis, median time to PSA progression was prolonged in the niraparib/AAP group compared to the placebo/AAP group among HRR+ patients (HR, 0.57; 95% CI, 0.43-0.76; nominal P<0.001).3
- In the BRCA1/2 subgroup, at the second interim analysis, median time to PSA progression doubled in the niraparib/AAP group (18.4 months) vs placebo/AAP group (9.2 months) (HR, 0.48; 95% CI, 0.33-0.70; nominal P<0.0001).5
- The ORR in the BRCA1/2 subgroup was 50.0% for niraparib/AAP vs 31.3% for placebo/AAP, yielding an RR for response of 1.60 (95% CI, 0.98-2.62; nominal P=0.053) and an RR for PSA response of 1.21 (95% CI, 1.02-1.43; nominal P=0.023).4
| NIRA/AAP | PBO/AAP | HR (95% CI) | P-Value | |
|---|---|---|---|---|
| BRCA1/2 Subgroupb | (n=113) | (n=112) | ||
| Median time to PSA progression, months | 18.4 | 9.2 | 0.46 (0.30-0.69) | Nominal P<0.001c |
| ORR, % | 50.0 | 31.3 | 1.60d (0.98-2.62) | Nominal P=0.053c |
| PSA response, n (%) | 93 (82.3) | 77 (68.8) | 1.21d (1.02-1.43) | Nominal P=0.023c |
| Confirmed | 89 (78.8) | 73 (65.2) | - | - |
| Unconfirmed | 4 (3.5) | 4 (3.6) | - | - |
| HRR+ Cohorta | (n=212) | (n=211) | ||
| Median time to PSA progression, months | 18.5 | 9.3 | 0.57 (0.43-0.76) | Nominal P<0.001c |
| Abbreviations: AAP, abiraterone acetate with prednisone; CI, confidence interval; HRR, homologous recombination repair; NE, not evaluable; NIRA, niraparib; ORR, objective response rate; PBO, placebo; PSA, prostate-specific antigen; RR, relative risk. aAt the first interim analysis. bAt the second interim analysis. cThese endpoints were not adjusted for multiple comparisons. Therefore, the p-value is nominal and statistical significance has not been established. dRR; RR>1 favors active treatment. | ||||
References
| 1 | Janssen Research & Development, LLC. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for treatment of participants with metastatic prostate cancer (MAGNITUDE). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2024 June 24]. Available from: https://clinicaltrials.gov/show/NCT03748641. NLM Identifier: NCT03748641. |
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