Lenvatinib (3) – Lenvima®

Adult patients with progressive, locally advanced or metastatic differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC) that has not responded to radioiodine therapy (RAI)

• There is no additional benefit of lenvatinib as monotherapy in adult patients with progressive, locally advanced or metastatic differentiated (papillary/follicular/Hürthle-cell) thyroid carcinoma (DTC) that has not responded to radioiodine therapy (RAI) is not proven compared with sorafenib.
• mortality
  • In the mortality category, the available data on the overall survival endpoint are subject to such a high degree of uncertainty that no valid conclusions can be drawn regarding the additional benefit of lenvatinib over sorafenib.
  • As in both studies a high proportion of patients from the placebo arm switched to the intervention arm following disease progression (SELECT: 88% as at the data cut-off date of 15 June 2014; DECISION: 77% at the final data cut-off date of 30 August 2017), the endpoint-specific risk of bias for the overall survival results in both studies is assessed as high.
  • Consequently, the adjusted analyses for the endpoint of overall survival must also be regarded as potentially highly biased due to the inherent high levels of uncertainty associated with treatment switching.
• morbidity
  • Data are available only for the DECISION study in the categories of morbidity and health-related quality of life.
  • Consequently, no data are available in these categories for an indirect comparison.
• Health-related quality of life
  • Data are available only for the DECISION study in the categories of morbidity and health-related quality of life.
  • Consequently, no data are available for an indirect comparison in these categories.
• Side effects
  • For the endpoints in the ‘side effects’ category, the pharmaceutical manufacturer did not provide time-adjusted analyses for the indirect comparison, but rather analyses based on the proportion of patients experiencing an event.
  • As there was a marked difference in the median duration of treatment between the study arms in both trials (SELECT: 13.8 vs. 3.9 months; DECISION: 10.6 vs. 6.5 months), these analyses cannot be used to draw valid conclusions regarding the additional benefit of lenvatinib over sorafenib due to insufficient certainty of the results.
• Conclusion
  • There are no suitable data available for an adjusted indirect comparison between lenvatinib and sorafenib from the DECISION and SELECT studies; consequently, the indirect comparison cannot be used to derive any additional benefit for the purposes of this assessment.
  • In the mortality category, the data for the indirect comparison of the overall survival endpoint are characterised by such a high degree of uncertainty – due to the high proportion of patients who switched from the control arm to the intervention arm – the data for the indirect comparison regarding the endpoint of overall survival are subject to such a high degree of uncertainty that no valid conclusions can be drawn regarding the additional benefit of lenvatinib over sorafenib.
  • In the categories of morbidity and health-related quality of life, data for an indirect comparison are available for only one side of the indirect comparison (the DECISION study).
  • In the category of side effects, the analyses submitted by the pharmaceutical manufacturer cannot be used due to insufficient certainty of the results.
  • There is no additional benefit of lenvatinib as monotherapy in adult patients with progressive, locally advanced or metastatic differentiated (papillary/follicular/Hürthle-cell) thyroid carcinoma (DTC) that has not responded to radioiodine therapy (RAI) is therefore not proven compared with sorafenib.
• Overall review
  • Overall, therefore, there are no suitable data from the DECISION and SELECT trials for the adjusted indirect comparison between lenvatinib and sorafenib, meaning that this indirect comparison cannot be used to infer any additional benefit.
  • The additional benefit of lenvatinib over sorafenib is not proven.

Courtesy translation only, please refer to the German original.