1.1 Entrectinib is recommended for use within the Cancer Drugs Fund as an option for treating neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours in adults and children 12 years and older if:
the disease is locally advanced or metastatic or surgery could cause severe health problems and
they have not had an NTRK inhibitor before and
they have no satisfactory treatment options.
It is recommended only if the conditions in the managed access agreement for entrectinib are followed.
1.2 This recommendation is not intended to affect treatment with entrectinib that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. For children and young people, this decision should be made jointly by the clinician and the child or young person or their parents or carers.
Why the committee made these recommendations
There is no standard treatment for NTRK fusion-positive solid tumours, so current treatment is based on where in the body the cancer starts. Entrectinib is a histology-independent treatment. This means that it targets a genetic alteration, NTRK gene fusion, that is found in many different tumour types irrespective of where the cancer starts.
Evidence from trials suggests that tumours with NTRK gene fusions shrink in response to entrectinib, but longer follow up is needed. It is difficult to know how well entrectinib works because it has not been compared with other treatments in trials. Also, there is evidence that entrectinib works well for some types of NTRK fusion-positive tumour, but little or no evidence for other types.
The cost-effectiveness estimates for entrectinib are uncertain because of limitations in the data. Some of these estimates are higher than what NICE normally considers an acceptable use of NHS resources so entrectinib cannot be recommended for routine use in the NHS.
Collecting more data on entrectinib would help to address some of the uncertainty in the evidence. Entrectinib has the potential to be cost effective given the company's commercial offer as part of a managed access agreement and using the diagnostic testing costs provided by NHS England. Therefore, entrectinib is recommended for use in the Cancer Drugs Fund.