Advice on a potential candidate for conditional inclusion of entrectinib (Rozlytrek®) for solid tumours with NTRK gene fusion

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.

Conditional inclusion

Based on these conclusions, we recommend that entrectinib should be designated as a potential candidate for VT (conditional inclusion).

If the Minister follows this recommendation, the Zorginstituut asks the parties to formulate their plans in greater detail and to draw up a covenant setting out the agreements needed to ensure that the VT (conditional inclusion) process is conducted carefully and successfully. The Ministry of Health, Welfare and Sport will have to conclude a financial arrangement with the marketing authorisation holder. 

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