NICE Recommends Enhertu for HER2-Low Breast Cancer

NICE has issued final draft guidance recommending trastuzumab deruxtecan (Enhertu) as a routine NHS option for HER2-low breast cancer, reversing its earlier decision not to fund the drug. The treatment from Daiichi Sankyo is the first licensed therapy aimed specifically at people whose tumours carry low levels of the HER2 protein, a group that was previously treated as HER2-negative.

Under the recommendation, the drug can be used within its marketing authorisation for adults with HER2-low metastatic or unresectable breast cancer who have had chemotherapy in the metastatic setting, or whose disease returned during adjuvant chemotherapy or within six months of finishing it. Funding depends on the company supplying the drug through its commercial access arrangement, which includes a confidential discount.

The turnaround follows a rapid review of the original guidance. NICE first considered the drug for this group in technology appraisal TA992 and declined to recommend it. Daiichi Sankyo then submitted a revised cost-effectiveness analysis with an updated commercial deal and updated EQ-5D-5L utility values, which the external assessment group validated and a subset of the committee considered.

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HER2-low breast cancer: a newly defined subgroup

HER2-low breast cancer is a subgroup that was previously classified as HER2-negative. These tumours score 1+ or 2+ on immunohistochemistry testing, which means they express small amounts of the HER2 protein without gene amplification. People in this group are currently offered treatments for HER2-negative disease, with the choice depending on whether the cancer is hormone-receptor positive or negative. Trastuzumab deruxtecan is an antibody drug conjugate that binds to the HER2 protein on these cells and delivers a chemotherapy payload directly to the tumour.

Patient organisations told the committee that metastatic breast cancer affects every part of a person’s life, physical, psychological, social and financial, and that the change in classification had created uncertainty about treatment options. Stakeholders noted that many people with the condition are of working age and care for young children or older relatives, and that the disease mainly affects women.

Evidence from DESTINY-Breast04

The clinical case rests on DESTINY-Breast04, an international, multicentre, randomised, open-label trial with seven UK centres. It compared trastuzumab deruxtecan against treatment of physician’s choice (TPC) in 557 people with HER2-low metastatic or unresectable breast cancer who had received one or two prior lines of chemotherapy. Most participants, 89%, had hormone-receptor positive disease and 11% had hormone-receptor negative disease. The comparator arm included 184 people, most of whom received eribulin (52%), with smaller shares getting capecitabine (21%), nab-paclitaxel (10%), gemcitabine (9%) and paclitaxel (8%).

Compared with TPC, trastuzumab deruxtecan delayed progression and extended survival. Progression-free survival improved with a hazard ratio of 0.5 (95% confidence interval 0.4 to 0.6) and overall survival with a hazard ratio of 0.6 (95% confidence interval 0.5 to 0.8), regardless of hormone-receptor status.

The economic case

The company modelled the drug against TPC using a partitioned survival model with three health states, a three-week cycle and a 30-year time horizon. After the committee raised concerns about how well the comparator arm reflected NHS practice, the company revised its analysis using a narrower DB04 NHS cohort that removed second-line eribulin and gemcitabine from the modelling, leaving 247 people in the trastuzumab deruxtecan arm and 118 in the TPC arm.

On extrapolation, the committee preferred the external assessment group’s approach, using a log-logistic distribution for TPC overall survival and a modified gamma for trastuzumab deruxtecan, with similar adjustments for progression-free survival and time to treatment stopping. The updated analysis valued EQ-5D-5L data from the trial directly using the UK EQ-5D-5L value set by Rowen et al. (2026), rather than mapping to the older 3L set.

Other assumptions included vial sharing that avoids waste in 75% of administrations, revised NHS administration costs from the 2023 to 2025 NHS Payment Scheme, and a £144 medical review cost for people receiving chemotherapy. A severity weight of 1.2 was applied to quality-adjusted life years.

Cost-effectiveness and the comparator

The committee concluded that the most likely cost-effectiveness estimate sits within the range NICE considers an acceptable use of NHS resources, agreeing an acceptable incremental cost-effectiveness ratio of around £35,000 per quality-adjusted life year gained. The exact figure is confidential because it depends on the discount.

The committee also looked at a cost-minimisation analysis against sacituzumab govitecan but concluded the unadjusted comparisons were too uncertain to support an assumption of equal clinical effectiveness, so it could not make a specific recommendation in the population eligible for both drugs.

Trastuzumab deruxtecan has a list price of £1,455 per 100 mg vial, excluding VAT, according to the BNF online accessed in September 2026. The commercial arrangement makes it available to the NHS with an undisclosed discount.

What it means for patients

In England, the NHS must fund the treatment for the recommended population if it is the most suitable option. Interim funding is available through the Cancer Drugs Fund from the point of marketing authorisation or the release of positive draft guidance, whichever is later, until 90 days after final publication, after which funding moves to routine commissioning. In Wales, the NHS must usually make the treatment available within 60 days of the first publication of the final draft guidance.

The committee recognised that trastuzumab deruxtecan is the first licensed treatment targeting HER2-low disease, and that quality of life benefits seen on the EORTC QLQ-C30 questionnaire, covering body image, sexual function and social function, may not be fully captured by the EQ-5D.

Source: NICE final draft guidance, trastuzumab deruxtecan for treating HER2-low metastatic or unresectable breast cancer after chemotherapy (September 2026)