Lenvatinib (Kisplyx, 2) – Kisplyx®

• Clinical trials
  • Study 205 was a randomised, open-label, actively controlled Phase 1b/2 trial.
  • In Study 205, a total of 153 patients were randomised to three study arms (lenvatinib + everolimus (51), lenvatinib (52) or everolimus (50)).
  • The METEOR trial is a randomised, open-label, actively controlled, Phase 3 trial comparing cabozantinib and everolimus.

Adult patients with advanced renal cell carcinoma (RCC) following prior treatment targeting vascular endothelial growth factor (VEGF)

• An additional benefit is not proven for lenvatinib in combination with everolimus.
• Overall, based on the data presented, no added benefit has been demonstrated for lenvatinib in combination with everolimus compared with cabozantinib for the treatment of adults with advanced renal cell carcinoma following prior treatment targeting the vascular endothelial growth factor (VEGF) has not been proven to provide an additional benefit.
• mortality
  • In the adjusted indirect comparison, there is no statistically significant difference between lenvatinib + everolimus and cabozantinib.
  • An additional benefit of lenvatinib plus everolimus in the mortality category is therefore not proven.
  • For the endpoint of overall survival, the adjusted indirect comparison shows no statistically significant difference between lenvatinib in combination with everolimus and cabozantinib.
• morbidity
  • In the adjusted indirect comparison, there is no statistically significant difference between lenvatinib in combination with everolimus and cabozantinib.
  • PFS is a composite endpoint comprising endpoints from the mortality and morbidity categories.
  • The endpoints mentioned were each assessed exclusively in the METEOR study; consequently, no adjusted indirect comparison can be carried out on the basis of these endpoints.
  • Consequently, no data on morbidity are available that could be used for an adjusted indirect comparison.
• Morbidity – Progression-free survival
  • Progression-free survival (PFS) was the primary endpoint in both the 205 study and the METEOR study.
  • In both studies, PFS was defined as the time from randomisation to radiologically confirmed disease progression or death from any cause.
• Morbidity – Symptoms (FKSI-DRS), Health Status (EQ-5D VAS), Skeletal-Related Events
  • The endpoints mentioned were each assessed exclusively in the METEOR study; consequently, no adjusted, indirect comparison can be carried out on the basis of these endpoints.
• quality of life
  • No data on health-related quality of life were collected in either the 205 study or the METEOR study.
• Side effects
  • With regard to side effects, the adjusted indirect comparison allows conclusions to be drawn only for the endpoints ‘severe AEs’ and ‘serious AEs’.
  • No statistically significant differences were observed between lenvatinib in combination with everolimus and cabozantinib.
  • In the overall review of the results on side effects, data from the adjusted indirect comparison are available only for the endpoints ‘severe AEs’ and ‘SAE’.
• Side effects – Adverse events
  • The results for the endpoint ‘total adverse events’ are presented for supplementary purposes only.
  • In both studies, all patients had experienced at least one adverse event.
• Side effects – serious AEs and severe AEs (CTCAE grade ≥ 3)
  • As already noted in the initial assessment, in Study 205, due to the small number of patients and the associated minor statistical power to identify statistically significant effects, both positive and negative effects may generally remain undetected.
  • Notwithstanding this, the adjusted indirect comparison for the endpoints of severe AEs (CTCAE grade ≥ 3) and SAE shows no statistically significant differences between lenvatinib in combination with everolimus and cabozantinib.
• Side effects – discontinuation due to AEs
  • For the endpoint ‘discontinuation due to AEs’, no adjusted indirect comparison is performed due to the open-label study design.
• Overall assessment
  • An adjusted indirect comparison provides patient-relevant results on mortality and adverse effects for the assessment of the additional benefit of lenvatinib in combination with everolimus for the treatment of adults with advanced renal cell carcinoma following prior treatment targeting the vascular endothelial growth factor (VEGF) provides patient-relevant results on mortality and side effects compared with the appropriate comparator therapy, cabozantinib, based on an adjusted indirect comparison.
  • This assessment follows the expiry of the limitations on the resolution of 16 March 2021. However, the conditions attached to the limitations were not met overall.
  • Overall, based on the data submitted, no additional benefit has been demonstrated for lenvatinib in combination with everolimus compared with cabozantinib for the treatment of adults with advanced renal cell carcinoma following prior treatment targeting the vascular endothelial growth factor (VEGF).

Courtesy translation only, please refer to the German original.