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Larotrectinib for treating NTRK fusion-positive solid tumours

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1 Recommendations

1.1

Larotrectinib should not be used as an option for treating neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours in people of all ages if:

  • the cancer is locally advanced or metastatic, or surgery could cause severe health problems and

  • there are no satisfactory treatment options.

1.2

This recommendation is not intended to affect treatment with larotrectinib that is currently funded by managed access (before final guidance publication). If this applies, NHS England and the company have an arrangement to make sure people who started treatment during the managed access period will continue to have larotrectinib until they and their NHS healthcare professional consider it appropriate to stop.

What this means in practice

Larotrectinib is not required to be funded and should not be used routinely in the NHS in England for the condition and population in the recommendations.

This is because there is not enough evidence to determine that larotrectinib offers benefits in this population.

Why the committee made these recommendations

This evaluation reviews the evidence for larotrectinib for treating NTRK fusion-positive solid tumours (NICE technology appraisal guidance 630). It also reviews new evidence collected during the managed access period, which includes evidence from clinical trials and from people having treatment in the NHS in England. 

There is no standard treatment for NTRK fusion-positive solid tumours, so treatment is based on where in the body the cancer starts. Larotrectinib targets a genetic alteration (NTRK gene fusion) that is found in many different tumour types (that is, tumours with different cellular characteristics, and tumours that start in different parts of the body). 

Clinical trial evidence suggests that tumours with NTRK gene fusions shrink in response to larotrectinib. But it is difficult to know how well larotrectinib works, because:

  • it was not compared with other treatments in the trials

  • the people in the trials did not fully reflect the people who would have larotrectinib in the NHS

  • there is evidence that larotrectinib works well for some types of NTRK fusion-positive tumour and less well for some other types, and for some tumour types there is little or no evidence.

Evidence from NHS practice also suggests that tumours with NTRK gene fusions shrink in response to larotrectinib. But this is uncertain because, due to the rarity of NTRK fusions, the evidence included only a small number of people and tumour types compared with what would be seen in the NHS.

There are concerns with the economic model. This is because it assumes that different tumour types in people of different ages would respond to larotrectinib in the same way, and there are uncertainties about: 

  • which clinical evidence to use in the model 

  • by how much larotrectinib increases how long people live 

  • how larotrectinib affects quality of life 

  • what treatment people have after larotrectinib and how much it costs 

  • how the cost-effectiveness results would differ if calculated for individual tumour types.

Because of the uncertainties in the clinical and economic evidence, it is not possible to determine the most likely cost-effectiveness estimates for larotrectinib. So, it should not be used.