Ipilimumab (2) – Yervoy®

a) Patients with BRAF V600 mutation-negative melanoma

• For patients with BRAF V600 mutation-negative unresectable or metastatic melanoma, additional benefit is not proven compared with the appropriate comparator therapy.
• On an overall assessment of the available results on mortality, quality of life and side effects, there is no conclusive evidence to support the assessment of additional benefit for ipilimumab compared with the appropriate comparator therapy.
• mortality
  • The available data are not suitable for demonstrating the additional benefit of ipilimumab compared with the appropriate comparator therapy for the endpoint of overall survival.
• morbidity
  • There is no evidence available to assess the additional benefit with regard to disease symptoms.
• quality of life
  • To present the results for the endpoint‘health-related quality oflife’, the results of the oncology-specific questionnaire EORTC QLQ-C30 were provided. On the ipilimumab side, this was collected only in the MDX010-20 and CA184-022 studies and compared with the results for dacarbazine (study CA184-024). Due to the high proportion of missing values, the very small proportion of patients included in the analysis and the non-adjusted indirect comparison, there is no conclusive evidence available to assess the additional benefit of ipilimumab compared with the appropriate comparator therapy. The pharmaceutical manufacturer did not claim any additional benefit for the endpoint ‘quality of life’.
• Side effects
  • When presenting the results for the endpoint ‘side effects’, the pharmaceutical manufacturer uses only data from prospective studies on the ipilimumab side, as retrospective studies are not conducted in accordance with the strict guidelines for RCTs and are therefore assumed to carry an increased risk of bias.
  • The comparison of overall rates is only available as a direct comparison (unadjusted) and therefore does not allow for any comparative conclusions. In addition, analyses of the time to event are available based on propensity score analyses. The limitations described under ‘Probability of additional benefit’ apply to this analysis.
  • There is therefore no conclusive evidence available for the endpoint ‘side effects’ to assess the additional benefit of ipilimumab compared with the appropriate comparator therapy.
• Conclusion
  • Taking the available results on mortality, quality of life and side effects into account as a whole, there is no conclusive evidence to assess the additional benefit of ipilimumab compared with the appropriate comparator therapy. On the basis of the evidence presented, an additional benefit is therefore not proven.

b) Patients with BRAF V600 mutation-positive melanoma

• For patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, additional benefit is not proven compared with the appropriate comparator therapy.
• There are no direct comparative studies available that examine ipilimumab against the appropriate comparator therapy, vemurafenib. To assess the additional benefit of ipilimumab compared with vemurafenib, the pharmaceutical manufacturer submitted a non-adjusted indirect comparison using dacarbazine as an indirect bridge comparator.
• The insufficient certainty of results identified for the indirect comparison between ipilimumab and dacarbazine (see assessment of additional benefit for patient group a) is further reduced by the subsequent non-adjusted comparison step. For this reason, the evidence submitted is not suitable for drawing conclusions regarding the additional benefit of ipilimumab compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.