The NHS in England is gearing up to review “revolutionary” cancer drugs that could “treat a wide range of cancers,” according to headlines today.

This new breed of cancer drug was singled out by the head of NHS England, Simon Stevens, in a speech to health leaders. They’re exciting because, unlike most cancer drugs, they’re designed to target specific changes in cancer cells’ DNA, rather than where the cancer is growing in the body. This means that patients with various different cancer types may be able to benefit from the drugs.

“It’s moving away from dividing up patients by disease type to looking for common molecular or genetic features within the tumours,” says Dr Matthew Krebs, an expert in precision medicine at the University of Manchester.

But while these drugs might become an important option for some patients, the genetic variations targeted are a lot less common than the headlines suggest.

And there’s plenty of work for the NHS to do before patients see the benefits of these new ‘tumour agnostic’ medicines – which is why Stevens announced that the NHS will be working with drug manufacturers in the coming months to get the NHS ready.

Why are these drugs special?

Drugs that target particular changes inside or on the surface of cancer cells aren’t new. And many are already used on the NHS to treat various cancers, the most famous being the breast cancer drug trastuzumab (Herceptin).

Like other targeted drugs, those named in today’s news – larotrectinib and entrectinib – take aim at cancer cells that carry a genetic change which can accelerate cancer growth. In the case of these drugs, that genetic change is called a NTRK fusion.

But unlike other targeted drugs, these precision treatments have been developed to target the fault regardless of where in the body the cancer is growing.

“The concept is that it doesn’t matter where the cancer develops, whether it’s in the bowel, breast, lung or a rarer cancer type – if you share the same underlying genetic abnormality then trials have shown you can get a response to this drug regardless of where the cancer is,” says Krebs.

These so-called ‘tissue agnostic’ drugs are being developed against several genetic abnormalities found in a range of cancers, but most of these are still in clinical trials. The furthest along are drugs targeting the NTRK fusion found in some cancers.

Who could benefit from these new drugs?

“If we put the TRK fusion in context it’s actually very rare,” says Krebs.

Less than 1 in 100 patients with more common cancer types will have the genetic alteration that might be targeted by the new drugs, he says. But there are some rare cancers, like a subtype of salivary gland cancer and certain children’s cancers, where almost all patients have the genetic change.

“For these rare cancers the drugs could have a very significant impact, because there aren’t many good existing therapies,” says Krebs.

Three quarters of the 55 patients taking larotrectinib as part of a trial spanning 17 cancers responded to the experimental drug, according to results published in 2018. Seven patients saw their cancer disappear completely and 34 patients’ cancers shrank after treatment. Updated results were presented at a recent cancer conference, with data from more patients showing a similar effect. But it’s not yet clear if some of these responses will turn in to long-term survival.

And in results presented at another recent cancer conference, 6 in 10 of the 54 adult cancers treated with entrectinib responded, with responses lasting an average of 10 months.

But as with lots of targeted drug treatments, the cancers can find a way to dodge the drug’s effects.

“We’ve seen some very good responses, but the treatments don’t work indefinitely, eventually the cancer develops resistance,” says Krebs. Drug companies are now developing new treatments that target these resistance mechanisms, with some already in clinical trials.

Finally, most side effects seen in trials were mild. Krebs says that although there are some side effects, “generally people tolerate the treatment very well”.

When will the drugs be available?

While exciting, today’s announcement doesn’t alter the fact that these drugs remain a long way off being routinely available for NHS patients.

Both larotrectinib and entrectinib are yet to be assessed by the National Institute for Health and Care Excellence (NICE) to determine if they offer enough value for money to be made available on the NHS. And as with any new treatment, the NHS will need to agree a price for both drugs. 

Added to this, neither drug has received the European licence needed before they can be looked at by NICE.

And crucially, even if the drugs are approved, their unusual nature could also cause challenges for the NHS in getting them to patients.

Challenges for the NHS

The clinical trials for these drugs have shown their effectiveness in patients with some cancer types, but that doesn’t mean the drugs won’t be effective in any others. Equally, the drugs haven’t been effective against all the cancer types they’ve been tested in. So NICE will need to work with the NHS to identify the right patients to receive the medicines.

There are a number of other questions that haven’t been resolved by clinical trials so far either.

Because the trials included patients who had already received varying numbers of other treatments, NICE can’t yet be sure how soon in a patient’s care the drugs should be considered, and where the drugs will provide the best value.

The trials also haven’t been running for long enough to give data on long-term outcomes, like how long patients taking the drugs live.

Another challenge is the availability of genetic testing. As these drugs target a particular genetic fault, patients’ tumours will need to be tested to determine if they could benefit from the treatment.

This adds an extra layer of complexity for the NHS. It will need to ensure doctors routinely test for the NTRK variation in everyone who could benefit, and that this test is available across the whole country.

Preparations are already underway to offer NTRK testing for patients diagnosed with some cancers, such as salivary gland cancer. But the test isn’t yet widely available and – depending on which cancer types the drug is ultimately approved for – the test may need to be expanded to more patients.

Planning is key. So it’s encouraging that the NHS is acknowledging these challenges and considering how to overcome them. This approach should prevent delays in tumour agnostic drugs reaching the small number of patients that could benefit, if and when they’re approved by NICE.

Duncan Sim is a policy advisor at Cancer Research UK