Entrectinib (1) – Rozlytrek®

• Clinical trials
  • The STARTRK-2 trial is a Phase II, uncontrolled clinical study that has been ongoing since November 2015.
  • In addition, the pharmaceutical manufacturer presents the single-arm entrectinib trials STARTRK-1, ALKA-372-001 and STARTRK-NG as supplementary information.

Adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) who have not been previously treated with ROS1 inhibitors

• An additional benefit of entrectinib over crizotinib is not proven.
• Overall, the data presented are not sufficient to demonstrate additional benefit over the appropriate comparator therapy, crizotinib; consequently, the additional benefit of entrectinib as monotherapy in adult patients with ROS1-positive, advanced NSCLC who have not previously received treatment with ROS1 inhibitors is not proven.
• mortality
  • To derive the additional benefit of entrectinib, the pharmaceutical manufacturer primarily draws on the results from the comparison with the Flatiron Health database for the endpoints of overall survival and PFS.
  • For the indirect comparisons presented, the observed effects are not large enough to rule out the possibility that they could be due exclusively to systematic bias.
  • The possibility of systematic bias in the results is indicated by the fact that the survival analyses for crizotinib-treated patients from the Flatiron Health database and the EUCROSS study differ significantly.
• morbidity
  • For further endpoints relating to morbidity and health-related quality of life, the dossier presents only the results of the STARTRK-2 study, without making a comparison with crizotinib.
• Health-related quality of life
  • For further endpoints relating to morbidity and health-related quality of life, the dossier presents only the results of the STARTRK-2 study, without making a comparison with crizotinib.
• Side effects
  • For the endpoint category ‘side effects’, the pharmaceutical manufacturer provides a descriptive comparison with crizotinib for selected side effects.
• Conclusion
  • For the benefit assessment, the pharmaceutical manufacturer presents the results from the STARTRK-2 registration trial involving adult patients with ROS1-positive NSCLC who had not previously received a ROS1 inhibitor.
  • The pharmaceutical manufacturer carries out a comparison exclusively with the appropriate comparator therapy for the endpoint of overall survival. For the indirect comparisons presented, the observed effects are not large enough to rule out the possibility that they might be due solely to systematic bias.
  • Furthermore, it is not possible to assess the additional benefit with regard to the endpoint categories of morbidity, quality of life and side effects compared with the appropriate comparator therapy on the basis of the indirect comparison provided.

Courtesy translation only, please refer to the German original.