Eribulin (1) – Halaven®

• Clinical trials
  • However, as part of the EMBRACE study on which the dossier is based, other oncological treatment methods were used in addition to the active ingredients in the appropriate comparator therapy.

a) for patients who can no longer be treated with taxanes or anthracyclines

• For patients whose disease has progressed following taxane- or anthracycline-and for whom further treatment with taxanes or anthracyclines is no longer an option, there is a hint of a minor additional benefit for eribulin in terms of overall survival compared with monotherapy with capecitabine or vinorelbine.
• The G-BA assesses this, taken as a whole, as a therapeutically significant additional benefit.
• With regard to the endpoint ‘overall survival’, the G-BA sees a therapeutically significant additional benefit for eribulin compared with the appropriate comparator therapy in population a).
• The G-BA therefore considers it justified, on balance, to classify the minor additional benefit as ‘minor’.
• The Federal Joint Committee (G-BA)’s benefit assessment is based solely on analyses derived from a single study, which, moreover, includes only minor numbers of patients in each of the relevant patient populations; and the results are therefore subject to a high degree of uncertainty, meaning that only a hint of a minor additional benefit can be established.
• mortality
  • In its dossier, the pharmaceutical manufacturer demonstrated, with statistical significance at two evaluation time points, an additional benefit for the endpoint of overall survival only for the overall population of the EMBRACE study.
  • In its benefit assessment report, IQWIG presented a summary analysis of the active ingredients in the appropriate comparator therapy, based on its own calculations using the data provided by the pharmaceutical manufacturer in the dossier. The result for the endpoint of overall survival is not statistically significant for either of the two analysis time points.
  • The division of this patient population into subpopulations a) and b) shows, in the benefit assessment report for the endpoint of overall survival, a statistically significant advantage for subpopulation a) at the first evaluation time point; at the second evaluation time point, the result was no longer statistically significant, but the same direction of effect was observed.
• Side effects
  • The pharmaceutical manufacturer also considered only the overall population when assessing adverse effects. The dossier contained no data that would have enabled an assessment analogous to that for overall mortality.
  • These data indicate a statistically significant higher risk of adverse effects for eribulin, including severe adverse events. For instance, according to the CTCAE classification of adverse events (Common Terminology Criteria for Adverse Events), eribulin is associated with a statistically significant higher number of events at severity grades 3 and 4.
  • Greater harm from eribulin compared with the appropriate comparator therapy in population a) cannot be ruled out due to the lack of available data.
  • However, the pharmaceutical manufacturer did not provide a breakdown of the adverse effects for this patient population; the G-BA therefore bases its assessment on the available analyses of the overall population (eribulin and TPC arms). In this context, significant adverse effects of eribulin must be taken into account.
• Health-related quality of life
  • These subsequently submitted analyses relate only to the endpoint of overall survival and not to other relevant endpoints such as health-related quality of life or toxicity data.
  • Furthermore, no data on health-related quality of life are available.
• Overall assessment
  • The G-BA therefore considers it justified, on balance, to classify the additional benefit as minor.

b) for patients who are eligible for re-treatment with taxanes or anthracyclines (docetaxel, doxorubicin, epirubicin, paclitaxel)

• For patients who are eligible for re-treatment with taxanes or anthracyclines, there is a hint that the benefit of the medicinal product is less than that of the appropriate comparator therapy.
• For this patient population (b), there is no statistically significant advantage for eribulin in terms of overall survival at any point during the analysis.
• Given the increased risk of severe side effects for the overall population – based on the analyses of a study and the summary of product characteristics (SmPC) for eribulin – and the fact that additional benefit is not proven compared with the appropriate comparator therapy, the Federal Joint Committee (G-BA)’s assessment procedure leads to the following conclusion: For patients who are eligible for re-treatment with taxanes or anthracyclines, there is a hint that the benefit of the medicinal product is less than that of the appropriate comparator therapy.
• mortality
  • For this patient population (b), there is no statistically significant advantage for eribulin in terms of overall survival at any point during the evaluation period.
• Side effects
  • Given the increased risk of severe side effects for the overall population – based on the analyses of a study and the summary of product characteristics (SmPC) for eribulin – and the lack of proof of additional benefit compared with the appropriate comparator therapy, the Federal Joint Committee (G-BA)’s assessment procedure concludes as follows: [...]
• Health-related quality of life
  • These subsequently submitted analyses relate only to the endpoint of overall survival and not to other relevant endpoints such as health-related quality of life or toxicity data.

Courtesy translation only, please refer to the German original.