Nivolumab (6) – Opdivo®

• Clinical trials
  • The CA209-205 trial is the registration trial for nivolumab in this therapeutic indication. Both trials are single-arm, open-label, non-comparative and multicentre in design.
  • The CA209-205 trial enrolled patients with cHL following unsuccessful ASCT.
  • The CA209-039 trial included patients with various treatment-refractory malignant haematological disorders.

a) Patients with relapsed or refractory classical Hodgkin lymphoma (cHL) following an autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin

• For patients with relapsed or refractory classical Hodgkin lymphoma (cHL) following an autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin, an additional benefit is not proven compared to the appropriate comparator therapy.
• In the absence of available RCTs, the pharmaceutical manufacturer drew on the single-arm nivolumab studies CA209-205 and CA209-039, as well as the retrospective Cheah 2016 study for the appropriate comparator therapy.
• A comparison of individual arms from the studies described is not suitable for drawing conclusions regarding the additional benefit of nivolumab compared with the appropriate comparator therapy, for the reasons set out below.
• The pharmaceutical manufacturer has not demonstrated that the population of the Cheah 2016 study is suitable for drawing conclusions regarding the additional benefit of nivolumab compared with the appropriate comparator therapy.
• It is unclear how many of the patients received the required prior treatment (ASCT followed by treatment with brentuximab vedotin).
• The comparability of the 2016 Cheah study with the nivolumab studies is further limited by the fact that the patients in the 2016 Cheahstudy were approximately 5 to 6 years younger than the patients in the nivolumab studies, and that a relatively large proportion of patients in the Cheah 2016 study were treated with experimental therapies that are difficult to quantify.
• As the pharmaceutical manufacturer has not provided data for the patient populations of interest (patients who were refractory or had relapsed following an ASCT and subsequent treatment with brentuximab vedotin), it has not demonstrated that the patient populations of interest in these studies are sufficiently similar.
• Furthermore, analyses comparing nivolumab with the appropriate comparator therapy are not available for all patient-relevant endpoints.
• Moreover, the effects are not of such a magnitude that they cannot be explained solely by the influence of confounding factors.
• Overall assessment / Conclusion
  • As there are no relevant data available overall for assessing the additional benefit of nivolumab, the additional benefit is not proven.

Courtesy translation only, please refer to the German original.