Niraparib / Abirateronacetat (1) – Akeega®

• Clinical trials
  • The pharmaceutical manufacturer submitted data for benefit assessment from the randomised, double-blind Phase IIIMAGNITUDE trial, in which niraparib/abiraterone acetate in combination with prednisone or prednisolone was compared with placebo in combination with abiraterone acetate and prednisone or prednisolone.

a) Adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic), for whom chemotherapy is not clinically indicated and who have not received prior treatment for mCRPC

• Consequently, the G-BA has determined that niraparib/abiraterone acetate in combination with prednisone or prednisolone for the treatment of adults with mCRPC and BRCA1/2 mutations (germline and/or somatic), for whom chemotherapy is not clinically indicated and who have not previously received treatment for mCRPC, a considerable additional benefit compared with abiraterone acetate in combination with prednisone or prednisolone.
• Based on the available evidence, the certainty of the evidence is therefore classified as ‘hint’.
• mortality
  • For the endpoint of overall survival, a statistically significant advantage was observed in the patient population relevant to the assessment—those for whom chemotherapy was not clinically indicated—in favour of niraparib/abiraterone acetate in combination with prednisone or prednisolone compared with the control arm.
  • The extent of the advantage achieved in overall survival is assessed as a marked improvement.
  • In the subgroup analyses for the endpoint of overall survival, an effect modification was observed based on the characteristic ‘previous taxane-based chemotherapy’ (yes vs. no; p = 0.029).
  • In its assessment of this subgroup analysis, the G-BA concludes that the interpretation of this effect modification is subject to significant uncertainties.
• Morbidity – radiographic progression-free survival (rPFS)
  • In the MAGNITUDE study, rPFS was defined as the time from the date of randomisation to the date of radiological progression or death, whichever occurred first.
  • For rPFS, there is a statistically significant advantage in favour of niraparib/abiraterone acetate in combination with prednisone or prednisolone.
  • The rPFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
• Morbidity – Symptomatic progression
  • Symptomatic progression is therefore generally regarded as a patient-relevant event.
  • However, uncertainties remain as to which events were included in the ‘other cancer-related interventions’ component.
  • Furthermore, the operationalisation chosen by the pharmaceutical manufacturer (retrospective recording of an intervention based on symptoms) is regarded as insufficient to capture events of symptomatic progression with adequate sensitivity.
• Morbidity – Pain (BPI-SF)
  • For the endpoint of ‘most severe pain’, assessed using item 3 of the BPI-SF, there is no statistically significant difference between the treatment arms.
  • For the endpoint ‘impairment due to pain’, assessed using items 9a–g of the BPI-SF, there is also no statistically significant difference between the treatment arms.
• Morbidity – Health status (EQ-5D Visual Analogue Scale)
  • For the health status endpoint, assessed using the EQ-5D VAS, there was no statistically significant difference between the treatment arms.
• Health-related quality of life
  • Data on health-related quality of life were collected in the MAGNITUDE study using the FACT-P instrument.
  • There was no statistically significant difference in the overall FACT-P score between the treatment groups.
• Side effects – total adverse events (AEs)
  • Almost all patients in the MAGNITUDE study experienced an adverse event.
• Side effects – serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3), therapy discontinuations due to AEs
  • There were no statistically significant differences between the treatment arms for the endpoints SAE, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
• Side effects – Specific AEs
  • In detail, with regard to specific AEs, there was a statistically significant difference in favour of niraparib/abiraterone acetate in combination with prednisone or prednisolone for the endpoint of anaemia (severe AE).
• Overall assessment
  • For the endpoint of overall survival, there is a statistically significant advantage of niraparib/abiraterone acetate in combination with prednisone or prednisolone compared with abiraterone acetate in combination with prednisone or prednisolone.
  • Compared with abiraterone acetate in combination with prednisone or prednisolone, niraparib/abiraterone acetate in combination with prednisone or prednisolone results in a prolongation of overall survival, the extent of which is assessed as a significant improvement.
  • In the morbidity endpoint category, there is an advantage for niraparib/abiraterone acetate in combination with prednisone or prednisolone with regard to the endpoint of symptomatic progression.
  • With regard to patient-reported symptoms, assessed using the BPI-SF and EQ-5D VAS measurement tools, there are no differences between the treatment arms that are relevant to the assessment.
  • With regard to health-related quality of life, treatment with niraparib/abiraterone acetate in combination with prednisone or prednisolone showed neither positive nor negative effects.
  • With regard to side effects, there were no differences between the treatment arms that were relevant to the benefit assessment. In detail, a disadvantage was observed only for specific adverse events at the endpoint of anaemia (severe AE).

b) Adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic), for whom chemotherapy is not clinically indicated and who have already received prior treatment for mCRPC

• An additional benefit is not proven.
• For the treatment of adults with previously treated metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated, there are no data available to enable an assessment of additional benefit.

Courtesy translation only, please refer to the German original.