Entrectinib (2) – Rozlytrek®

• Clinical trials
  • The STARTRK-2 trial is a Phase II, uncontrolled clinical study that has been ongoing since November 2015.
  • The STARTRK-NG trial is an uncontrolled clinical study of Phase I/Ib non-controlled dose-escalation study, followed by a dose-extension phase, in paediatric and adult patients up to the age of 22 with relapsed or refractory solid extracranial tumours or primary tumours of the central nervous system with or without NTRK, C-ros oncogene 1 or anaplastic lymphoma kinase fusions.

Adult and paediatric patients aged 12 years and over with solid tumours harbouring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have locally advanced or metastatic disease or a condition where surgical resection has a high probability of resulting in severe morbidity, and who have not previously received an NTRK inhibitor and for whom no satisfactory treatment options are available

• The additional benefit of entrectinib over the appropriate comparator therapy is not proven.
• Consequently, the evidence provided does not allow for a comparison with the appropriate comparator therapy; therefore, no additional benefit of entrectinib as monotherapy has been demonstrated for the treatment of adult and paediatric patients aged 12 years and over with solid tumours harbouring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have locally advanced or metastatic disease or a condition where surgical resection has a high probability of resulting in severe morbidity, and for whom no satisfactory treatment options are available, is not proven.
• Overall assessment
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the results from the STARTRK-2 registration trial in adult patients with NTRK gene fusions, as well as data on paediatric patients from the STARTRK-NG trial regarding treatment with entrectinib.
  • The therapeutic indication for entrectinib covers various tumour entities and, consequently, tumour diseases with different courses and prognoses. The G-BA therefore considers it appropriate and necessary to assess the results separately for each tumour entity.
  • Data from the STARTRK-2 study are available for the latest data cut-off, covering a total of 21 tumour entities treated with entrectinib. The number of patients per tumour entity varies considerably, ranging from 1 to a maximum of 16 patients. Data from ≥ 10 patients are available for only three tumour entities: soft tissue sarcoma (N=11 NTRK EE; N=13 NTRK SE), non-small cell lung cancer (N=12 NTRK EE; N=14 NTRK SE) and secretory salivary gland carcinoma (N=12 NTRK EE; N=16 NTRK SE).
  • The registration trial is an uncontrolled clinical study and therefore does not include a control group. Overall, the evidence submitted by the pharmaceutical manufacturer to demonstrate additional benefit lacks a comparison with the appropriate comparator therapy.
  • The data on paediatric patients submitted by the pharmaceutical manufacturer are not suitable for assessing additional benefit in the present therapeutic indication.
• Conclusion
  • Consequently, the proof submitted does not allow for a comparison with the appropriate comparator therapy, which is why an additional benefit of entrectinib is not proven.

Courtesy translation only, please refer to the German original.