New breed of targeted cancer drug gets initial ‘no’ for NHS in England  

The National Institute for Health and Care Excellence (NICE) has ruled not to recommend the drug larotrectinib (Vitrakvi) for adults and children whose tumours test positive for a specific genetic change.

Larotrectinib is one of a new breed of cancer drugs designed to target specific changes in cancer cells’ DNA, rather than where the disease is growing in the body. This means that patients with various cancer types may stand to benefit from the treatment.  

The drug would have been available as a last line treatment for patients when all other options ‘have been exhausted’, making it a potential new treatment for advanced stage cancer patients or those with limited options.

The head of NHS England, Simon Stevens, singled out drugs like larotrectinib in a speech in June 2019, announcing that the NHS would ‘fast track’ the treatments. 

The drug will be looked at again by NICE in March. NICE are also reviewing a second drug, entrectinib, which works in the same way as larotrectinib and could be made available to the same group of patients if approved.

A new breed of treatment 

Larotrectinib is designed to target a specific change in cancer cells that speeds up cancer growth, called an NTRK fusion. The treatment aims to shrink tumours, potentially enough to make surgery an option for patients whose cancer could not otherwise be treated in this way. 

NTRK gene fusions are rare in common types of cancer, occurring in less than 1 in 100 people with breast, bowel or lung cancer. But the DNA error may occur in more than 90 in 100 patients with some rare tumour types, such as infantile fibrosarcoma.

NICE estimates that between 600 and 700 people will have tumours with this particular genetic change. 

Patients must be tested for NTRK fusion before being treated with larotrectinib. NHS England estimates that 100,000 patients a year will eventually be tested for the mutation, though initially testing will only be offered after all other treatment options have been exhausted. 

Concerns over trial data

Evidence collected from 3 clinical trials suggests tumours with NTRK gene fusions often shrink in response to larotrectinib. 

But NICE raised some key concerns with the data provided by the trials, which made it harder to judge the treatment’s benefits. 

“This type of drug is unusual because it can be used to treat several different cancers and the genetic change it targets is rare, so the task of judging how much it could help NHS patients is very complicated,” says Gray. 

As the trials involved very small numbers of adults and children with many different cancer types, the drug’s benefits weren’t directly tested against any standard treatments. 

NICE also said the trials didn’t provide enough data to estimate how the effects of larotrectinib might vary across patients with different cancer types. 

There were also concerns that patients with rarer cancers were overrepresented in the clinical trials compared to the people who would be treated with larotrectinib in an NHS setting. And the trials did not include any patients with some cancer types where larotrectinib might be used in the NHS.  

Lastly, NICE highlighted that there wasn’t enough evidence around the long-term benefits of larotrectinib in improving survival. 

All of this uncertainty meant NICE couldn’t be confident the treatment would be cost-effective. As a result, their initial guidance is that the drug shouldn’t be offered on the NHS in England.

NICE decisions are usually adopted in Wales and Northern Ireland as well as England, so the decision is likely to affect patients in all three nations. Scotland has a separate process for reviewing drugs.

Next steps 

As this is NICE’s first decision about whether to recommend the drug for funding, there will now be an opportunity for others to comment on the decision. 

This will also allow the manufacturer to respond to the uncertainties NICE has highlighted and provide additional information. John Stewart, NHS national director of specialised commissioning, said “the NHS’ door remains open for further discussion.”

The expert committee will meet again in March to decide whether any new information is enough to change their final recommendation. 

“We urge the drug’s manufacturer, NICE and NHS England to continue to work together to resolve these issues, so that patients can access the drug as quickly as possible,” says Gray. 

“In the meantime, it’s crucial the NHS continues to prepare for this new type of drug by ensuring genetic testing is available across the country to identify patients who could benefit from targeted cancer drugs like this one.”