Niraparib / Abirateronacetat (2) – Akeega®

• Clinical trials
  • The AMPLITUDE trial is an ongoing, double-blind, randomised, controlled Phase III trial comparing niraparib/abiraterone acetate in combination with placebo, prednisone and ADT against the combination of placebo, abiraterone acetate, prednisone and ADT.

a) Adult patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) with BRCA1/2 mutations (germline and/or somatic) and a high-risk profile

• On balance, the improvement in the morbidity endpoint ‘symptomatic progression’ – which is regarded as relevant but, based on the available data, no more than a minor improvement – is offset by significant disadvantages in terms of side effects.
• In a cost-benefit analysis, the G-BA concludes that no additional benefit has been demonstrated for niraparib/abiraterone acetate in combination with prednisone or prednisolone and ADT, compared with abiraterone acetate in combination with prednisone or prednisolone and ADT, an additional benefit is not proven.
• mortality
  • No statistically significant difference was observed between the treatment groups for the endpoint of overall survival.
• Morbidity – Symptomatic progression
  • The composite endpoint of symptomatic progression was defined, in accordance with Protocol Amendment 4 of 28 August 2023, as the time from randomisation to the first documented occurrence of any of the following events: the use of radiotherapy for skeletal or pelvic symptoms; the need for tumour-related orthopaedic surgery; cancer-related morbidity events (for example: fractures [symptomatic and/or pathological], spinal cord compression, urinary tract obstructions), initiation of a new systemic cancer treatment due to cancer symptoms, or other cancer-related procedures (e.g. insertion of a nephrostomy, insertion of a urinary catheter, or surgery for tumour symptoms).
  • In summary, an improvement in the endpoint of symptomatic progression, and thus an advantage for niraparib/abiraterone acetate in combination with prednisone and ADT compared with abiraterone acetate in combination with prednisone and ADT can be observed.
  • However, uncertainties remain regarding the consideration of the sub-endpoint ‘death from any cause’. Taking into account the total number of events, the absolute difference between the treatment groups and the number of events in the respective individual endpoints, the results for the endpoint of symptomatic progression are assessed as relevant but, based on the available data, no more than a minor improvement.
  • In this regard, analysis A2) is used for the present assessment, which shows a statistically significant advantage for niraparib/abiraterone acetate in combination with prednisone and ADT.
  • In addition, Analysis A1), which includes the sub-component ‘death from any cause’, shows a similar trend, although this is not statistically significant (hazard ratio [95% CI]; p-value: 0.67 [0.39; 1.15]; p-value: 0.143).
• Morbidity – Most severe pain (BPI-SF Item 3), impairment due to pain (BPI-SF Items 9a–g) and health status (EQ-5D VAS)
  • For the endpoints of most severe pain (BPI-SF Item 3), pain-related impairment (BPI-SF Items 9a–g) and health status, as assessed using the EQ-5D VAS, no statistically significant difference was observed between the treatment groups.
• quality of life
  • In the AMPLITUDE study, patients’ quality of life is assessed using the FACT-P total score.
  • No statistically significant difference was observed between the treatment groups.
  • Overall, therefore, there is neither an advantage nor a disadvantage to niraparib/abiraterone acetate in combination with placebo, prednisone and ADT in terms of health-related quality of life.
• Side effects – serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3)
  • For the endpoints ‘Serious AEs (SAEs)’ and ‘Severe AEs (CTCAE grade ≥ 3)’, a statistically significant difference was observed in each case to the disadvantage of niraparib/abiraterone acetate in combination with placebo, prednisone and ADT.
• Side effects – Discontinuation due to side effects (≥ 1 active component)
  • For the endpoint ‘discontinuation due to AEs (≥ 1 active ingredient)’, no statistically significant difference was observed between the treatment groups.
• Side effects – anaemia and hypertension (severe side effects in each case)
  • For the endpoints of anaemia and hypertension (both PTs and severe AEs), there was a statistically significant difference in favour of niraparib/abiraterone acetate in combination with placebo, prednisone and ADT that is associated with a disadvantage.
• Overall assessment
  • For the endpoint of overall survival, there was no statistically significant difference between the treatment groups.
  • For the combined endpoint ‘symptomatic progression’ – which encompasses various clinically relevant events based on symptoms – an improvement, and thus an advantage, can be observed for niraparib/abiraterone acetate in combination with prednisone and ADT compared with abiraterone acetate in combination with prednisone and ADT.
  • However, uncertainties remain regarding the inclusion of the sub-component ‘death from any cause’. The results for the endpoint ‘symptomatic progression’ are assessed as a relevant improvement, though no more than a minor one.
  • With regard to health-related quality of life, treatment with niraparib/abiraterone acetate in combination with prednisone and ADT shows neither positive nor negative effects.
  • With regard to side effects, a significant disadvantage was observed for treatment with niraparib/abiraterone acetate in combination with prednisone and ADT, attributable to a marked increase in SAE and severe AEs (CTCAE grade ≥ 3).
  • With regard to specific AEs, a significant increase in severe anaemia and severe hypertension is evident in detail.
  • On balance, the improvement in the morbidity endpoint ‘symptomatic progression’ is offset by significant disadvantages in terms of side effects.
  • In a risk-benefit assessment, the G-BA concludes that no additional benefit has been demonstrated for niraparib/abiraterone acetate in combination with prednisone or prednisolone and ADT, compared with abiraterone acetate in combination with prednisone or prednisolone and ADT, an additional benefit is not proven.

b) Adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) and BRCA1/2 mutations who are not newly diagnosed and/or do not have a high-risk profile

• No data are available for the group of patients with metastatic hormone-sensitive prostate cancer (mHSPC) and BRCA1/2 mutations who are not newly diagnosed and/or do not have a high-risk profile.
• Consequently, additional benefit for niraparib/abiraterone acetate in combination with prednisone or prednisolone and ADT is not proven.

Courtesy translation only, please refer to the German original.