Follow-up advice on conditional inclusion of entrectinib (Rozlytrek®)

Zorginstituut Nederland recommends the Minster for Medical Care that entrectinib (Rozlytrek®) should be conditionally included in the basic health care package for treating adult patients and children aged 12 and over with solid tumours (cancer) that express a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This is a follow-up advise to the previous recommendation that entrectinib should be designated as a potential candidate for VT (conditional inclusion).

Zorginstituut's advice

Entrectinib is licensed for treating adult patients and children aged 12 and over with solid tumours (cancer) that express a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Entrectinib is an NTRK inhibitor with a tumour-agnostic indication. A tumour-agnostic medicine is a medicinal product that is used against tumours that exhibit a specific genetic mutation, irrespective of the location of the tumour. This is in contrast to the majority of medicinal products, which have been developed to treat tumours depending on the specific organ or tissue in which the tumour arose. 

It was not possible to determine whether the medicinal product entrectinib (Rozlytrek®) complies with established medical science and medical practice. The current assessment framework is not sufficient at this time for this type of medicinal product (tumour-agnostic medicines). The parties in the field see entrectinib as a highly promising drug.

The broadening of the policy framework for VT (conditional inclusion) of tumour-agnostic medicinal products means that entrectinib meets the criteria imposed, namely: 

  • Entrectinib has been granted marketing authorisation by the EMA and has orphan drug and conditional status. 
  • It is a case of an unmet medical need. 
  • The marketing authorisation holder is the main applicant and this request is backed by an independent research institution, the physicians association and the patients' association.
  • Additional data will be collected during Phase 1 in the international studies that have been made mandatory by the EMA. Furthermore, the Dutch patients will be included in a register to ensure that the VT (conditional inclusion) research requirement is complied with.
  • After an assessment framework for tumour-agnostic medicinal products has been produced, the Zorginstituut will carry out a health care package assessment using the data gathered up to that point (including international data). 
  • If it is not possible to answer the package question after Phase 1, Phase 2 of the VT (conditional inclusion) process will have to commence.

The Zorginstituut recommends the Minister for Medical Care to include entrectinib conditionally in the basic health insurance package for a 3.5-year period, in order to start with Phase 1.

Following our previous advise of March 10, 2021 relevant parties made agreements in a covenant about additional data collection linked to conditional inclusion and about the settlement after the end of the conditional inclusion period. The Zorginstituut estimates that the agreements made provide sufficient guarantees for the conditional inclusion process to proceed carefully and successfully.

This report is a summary of recommendations by Zorginstituut Nederland. The original text is in Dutch.