Surprise Enhertu rejection follows NICE process change

NICE rejection
Joe Pee

NICE has rejected the use of AstraZeneca and Daiichi Sankyo’s Enhertu as an NHS treatment for advanced HER2-low breast cancer, a decision that the companies have described as “devastating”.

The decision covers the use of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy

At a stroke, the decision sets up a disparity in access to therapy within the UK, as Enhertu was backed for this use by the Scottish Medicines Consortium (SMC) last December. It is also reimbursed for this indication in 13 other countries in Europe, including Germany and Italy, as well as in Canada.

AZ estimates that around 1,000 patients in England alone will now miss out on treatment with Enhertu, and patient organisation Breast Cancer NOW described the outcome as a “dark day”, denying patients the chance of “more time to live and more time before their disease progresses, compared to chemotherapy.”

AZ's UK president, Tom Keith-Roach, said the rejection stemmed from “the rigid application of a flawed methodology” that has “been prioritised ahead of doing what’s right for breast cancer patients in England and Wales.”

At the heart of the company’s concern is NICE’s use of a disease severity modifier, introduced two years ago, which can change the threshold for cost-effectiveness in appraisals. In simplified terms, it introduces a weighting based on the number of years a patient may survive with a disease and the number of years lost as a result.

Previously, NICE committees could recommend treatments with a higher cost for people with rare diseases who were in the last months of their life (the end-of-life or EOL modifier), but the new approach introduces a ‘willingness to pay’ weighting across a broader range of disease areas.

That effectively means that quality-adjusted life years (QALYs) – a standard unit for cost-effectiveness calculations – are no longer always considered to have the same value in decision-making, with a greater value on QALY gains in severe diseases. Scotland has retained the use of EOL criteria in its appraisals.

Enhertu – which is the first end-of-life breast cancer treatment to go through the new appraisal process – becomes the first breast cancer therapy to be turned down by NICE in five years.

“We call on NICE to both reverse their decision and expedite an update to their new severity modifier, which clearly isn’t working in the interests of patients,” said Keith-Roach.

Enhertu was approved for this indication on the strength of the DESTINY-Breast 04 trial, which found that the drug offered an additional 4.8 months of progression-free survival (PFS) than chemotherapy (9.9 versus 5.1 months) and an additional 6.4 months of overall survival (23.9 versus 17.5 months).

Breast Cancer NOW has launched a petition and awareness campaign calling for an urgent review by NICE of the impact of its new methods for evaluating health technologies under the #EnhertuEmergency hashtag. 

NICE issued a statement saying that a key uncertainty in estimating Enhertu’s cost-effectiveness was how much longer people on Enhertu live compared with those receiving standard treatment in the future.

"Despite accounting for the condition’s severity by applying a severity modifier, and accounting for innovation and uncaptured benefits, the cost the NHS was being asked to pay was too high in relation to the benefits it provides for it to be recommended for routine use in the NHS," said Helen Knight, director of medicines evaluation at the health technology assessment (HTA) agency.

“Without a commercial arrangement that results in a price that represents a cost-effective use of NHS resources, NICE cannot recommend Enhertu."

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