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

Zorginstituut Nederland recommends that larotrectinib should be designated as a potential candidate for conditional inclusion. Larotrectinib is licensed for treating adult patients and paediatric patients with solid tumours (cancer) that express a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. 

Zorginstituut's advice

Larotrectinib is licensed for treating adult patients and paediatric patients with solid tumours (cancer) that express a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Larotrectinib 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. 

After an initial discussion in the Scientific Advisory Board (WAR), the Zorginstituut concluded that the drug is so innovative that it is not possible to determine whether the medicinal product larotrectinib (Vitrakvi®) 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 larotrectinib as a highly promising drug.

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

  • Larotrectinib 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 occupational group 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 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 conditional inclusion process will have to commence.

Conditional inclusion

Based on these conclusions, we recommend that larotrectinib 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.