Abirateronacetat (1) – Zytiga®

a) Patients with metastatic castration-resistant prostate cancer who have progressed during or after chemotherapy containing docetaxel and for whom further treatment with docetaxel is no longer an option

• For patients whose disease has progressed during or after chemotherapy containing docetaxel and for whom further treatment with docetaxel is no longer an option, there is an indication of considerable additional benefit compared with the appropriate comparator therapy.
• The certainty of the evidence (probability of additional benefit) is classified as ‘indication’.
• The G-BA classifies the extent of the additional benefit of abiraterone acetate for the ‘Best Supportive Care’ population as considerable, based on the criteria set out in Section 5(7) of the AM-NutzenV.
• Compared with the appropriate comparator therapy ‘Best Supportive Care’, this constitutes a significant improvement in treatment-related benefit that has not previously been achieved, in accordance with Section 5(7) in conjunction with Section 2(3) of the AM-NutzenV, as a moderate prolongation of survival (endpoint ‘overall survival’) is achieved.
• Based on these considerations, the additional benefit is more than a minor additional benefit. However, a classification as a major additional benefit is not justified.
• This uncertainty regarding the study data on the endpoints ‘time to first skeletal event’ and ‘time to pain progression’ does not affect the overall assessment of the extent of the additional benefit.
• Mortality – Overall survival
  • Compared with the appropriate comparator therapy ‘best supportive care’, this represents, in accordance with Section 5(7) in conjunction with Section 2(3) of the AM-NutzenV, a significant improvement in treatment-related benefit not previously achieved, as a moderate prolongation of survival (endpoint “overall survival”) is achieved.
• Morbidity – time to first skeletal event
  • For the patient-relevant endpoint ‘time to first skeletal event’, the additional benefit of abiraterone acetate can only be assessed to a limited extent due to insufficient data on the bisphosphonates used as concomitant medication, which may influence the occurrence of skeletal events.
  • In the underlying study (COU-AA-301), 4% of patients were being treated with bisphosphonates prior to the start of the study. During the course of the study, the proportion of patients treated with bisphosphonates rose to 43% in the abiraterone acetate arm and 49% in the placebo arm (see FDA: Clinical Review of NDA 202379. Zytiga™ (abiraterone acetate) for Metastatic Castration-Resistant Prostate Cancer after Prior Chemotherapy, 2011, p. 45).
  • No information regarding the indication, dosage or duration of bisphosphonate treatment was provided by the pharmaceutical manufacturer.
• Morbidity – time to pain progression
  • For the patient-relevant endpoint ‘time to pain progression’, the additional benefit of abiraterone acetate cannot be conclusively assessed.
  • As part of ‘best supportive care’ for patients with metastatic castration-resistant prostate cancer, structured pain management is routinely provided. In the underlying study (COU-AA-301), in addition to the data from the pain scale, analgesic consumption was measured in accordance with the WHO scale.
  • The study recorded a 30% increase in analgesic consumption. As pain management was at the discretion of the treating doctor, there was no blinding of pain medication, and specific details on pain management are lacking, the results for the ‘pain’ endpoint are of limited methodological validity (see IQWiG dossier assessment on abiraterone acetate A11-20, p. 44; dossier submitted by the pharmaceutical manufacturer, Module 4 A, p. 88; Minutes of the oral hearing on the active ingredient abiraterone acetate, 7 February 2012).
• Side effects
  • With regard to the aspect of side effects, the dossier assessment provides no indications of significant harm resulting from serious adverse events associated with abiraterone acetate.
  • In the G-BA’s assessment, a downgrading of the extent of the additional benefit does not appear warranted.

b) Patients with metastatic castration-resistant prostate cancer who have progressed following docetaxel-containing chemotherapy but who are, in principle, still eligible for further docetaxel-containing chemotherapy

• For patients who have progressed following docetaxel-based chemotherapy and for whom further treatment with docetaxel is an option, additional benefit is deemed not proven, as the necessary proof was not submitted in full by the pharmaceutical manufacturer at the relevant time (Section 35a(1), fifth sentence, of Book V of the Social Code).
• In the present case, the search of trial registers required for the assessment of additional benefit is lacking.
• As the pharmaceutical manufacturer has not provided evidence of a search of trial registries, the completeness of the pool of studies cannot be assessed.
• The pharmaceutical manufacturer has not fulfilled the statutory requirement to submit the necessary evidence in full at the relevant time. The dossier must therefore be regarded as incomplete. Pursuant to Section 35a(1), fifth sentence, of SGB V, this means that the additional benefit of abiraterone acetate compared with the appropriate comparator therapy, docetaxel—re-treatment for patients whose disease has progressed following docetaxel-containing chemotherapy and for whom re-treatment with docetaxel is an option — is deemed not proven.

Courtesy translation only, please refer to the German original.