Abirateronacetat (2) – Zytiga®

Adult men with metastatic, castration-resistant prostate cancer whose disease is asymptomatic or mildly symptomatic following failure of conventional androgen deprivation therapy

• For adult men with metastatic, castration-resistant prostate cancer whose disease is asymptomatic or mildly symptomatic following failure of androgen deprivation therapy, and for whom chemotherapy is not yet clinically indicated, there is an indication of considerable additional benefit compared with the appropriate comparator therapy.
• The G-BA classifies the extent of the additional benefit of abiraterone acetate as considerable, based on the criteria in Section 5(7) of the AM-NutzenV, taking into account the severity of the disease and the therapeutic objective in the treatment of the disease.
• The certainty of the finding (probability of the additional benefit) is classified in the ‘indication’ category.
• On the basis of these considerations, the information in the dossier, the results of the benefit assessment and the expert opinions, the G-BA concludes that abiraterone acetate offers a considerable amount of additional benefit compared with conventional androgen deprivation therapy alone.
• mortality
  • The endpoint ‘overall survival’ was assessed as a co-primary endpoint in the COU-AA-302 study.
  • The median survival time for patients randomised to the abiraterone acetate arm was 35.3 months, which was statistically significantly 5.2 months longer than for patients randomised to the control arm.
  • With regard to the mortality endpoint, the G-BA assesses the extent of the additional benefit of abiraterone acetate as considerable, as a moderate prolongation of survival is achieved compared with conventional androgen deprivation therapy alone.
• Morbidity – Pain
  • Time to initiation of opioid therapy
  • In the COU-AA-302 study, the endpoint ‘severe pain’ was recorded from the start of opioid therapy and monitored beyond the treatment phase until the end of the follow-up period.
  • For the endpoint ‘time to initiation of opioid therapy’, a statistical advantage was observed for abiraterone acetate.
  • The prevention or reduction of severe pain is clinically relevant to patients.
  • The results for the endpoint ‘severe pain’, operationalised as the time to initiation of opioid therapy, are interpreted for abiraterone acetate as a delay in the onset of a serious symptom of the disease, which supports the considerable additional benefit demonstrated for the overall survival endpoint.
  • Brief Pain Inventory Short Form (BPI-SF)
  • The endpoint ‘pain’ was assessed as a patient-reported outcome using the BPI-SF questionnaire until the occurrence of progression terminating the treatment phase.
  • A statistical advantage for abiraterone acetate is evident for the endpoints ‘worst pain’ and ‘impairment due to pain’.
  • Opinions differ regarding the clinical relevance of the results. This does not affect the overall conclusion regarding the extent of the additional benefit.
  • Time to initiation of chemotherapy
  • In this study, the decision to initiate chemotherapy was not based on prospectively defined criteria, but on an individual doctor-patient decision.
  • The patient relevance of the endpoint ‘time to initiation of chemotherapy’ is therefore questionable, and it is not suitable for assessing additional benefit.
  • Time to deterioration in general condition
  • The endpoint ‘time to deterioration in general condition’, operationalised as a deterioration of at least one stage in the ECOG performance status, is therefore not suitable for assessing additional benefit.
• quality of life
  • In study COU-AA-302, data on disease-specific quality of life up to the occurrence of progression terminating the treatment phase were collected using the FACT-P patient questionnaire, which has been validated for the therapeutic indication of prostate cancer.
  • A statistical advantage for abiraterone acetate was observed for the endpoint ‘disease-specific quality of life’.
  • Opinions differ regarding the clinical relevance of the results. This does not affect the overall conclusion regarding the extent of the additional benefit.
• Side effects
  • The positive effects of abiraterone acetate are offset by adverse events.
  • In the abiraterone acetate arm, both the proportion of patients who experienced at least one adverse event (overall AE rate) and the proportion of patients who experienced at least one serious adverse event (overall SAE rate) were statistically significantly higher than in the control arm.
  • Given that the average duration of treatment with abiraterone acetate was significantly longer than with placebo, it is likely that the incidence of adverse events for abiraterone acetate has been overestimated.
  • With regard to side effects, there are no indications of greater harm from adverse events associated with abiraterone acetate that would justify downgrading the extent of the additional benefit.
• Overall assessment
  • Taking into account the available results on mortality, morbidity and quality of life, together with the findings on side effects, abiraterone acetate does not demonstrate a sustained and, compared with the appropriate comparator therapy, previously unachieved major improvement in treatment-related benefit; in particular, it does not result in a cure of the disease, no major prolongation of life, no long-term freedom from severe symptoms and no substantial avoidance of serious side effects.
  • Therefore, classification as ‘major additional benefit’ is not justified.
  • The findings on overall mortality, supported by the findings on the serious symptom of severe pain – operationalised as time to the start of opioid therapy – are assessed as a clear improvement in treatment-related benefit that has not yet been achieved with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.