National Institute for Health and Care Excellence (NICE) has recommended trastuzumab deruxtecan for use within the Cancer Drugs Fund (CDF) as an option for treating HER2-positive unresectable or metastatic breast cancer after one or more anti-HER2 treatments in adults.

In the UK, almost 54,000 cases of breast cancer in women are diagnosed annually, with an estimated one in five cases being HER2 positive.

The impact of the disease is significant, with breast cancer responsible for approximately 12,000 deaths per year.1 There are an estimated 35,000 people living with metastatic (where the cancer has spread) breast cancer in the UK, the disease has a poor prognosis and survivability.

“Today’s announcement is a step forward for people in England living with HER2-positive metastatic breast cancer,” said Jo Taylor, founder of METUP UK, an advocacy group for people living with metastatic breast cancer. “Though many treatment advances have been made to improve outcomes against this incurable disease, there remains a significant unmet need for patients who do not have a durable response to other available later-line options.”

“HER2 positive disease impacts one in five women with breast cancer and previously treated patients typically experience disease progression in less than a year with the historical standard of care treatment,” said Professor Peter Schmid, Barts Cancer Institute. “The DESTINY-Breast03 trial showed that trastuzumab deruxtecan improved survival compared to trastuzumab emtansine, further highlighting its potential to redefine the treatment of HER2 positive metastatic breast cancer.”

The NICE FDG decision was based on the first interim analysis of the DESTINY Breast-03 trial. The positive results from the pivotal DESTINY-Breast03 phase 3 trial reviewed at the time of the NICE submission, showed that, at 12 months, the percentage of patients who were alive without disease progression, as assessed by blinded independent central review, was 75.28% (95% CI, 69.8 to 80.7) with trastuzumab deruxtecan as compared with 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine; the hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22 to 0.37; P<0.001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

“We are very proud to have worked in partnership with NICE, NHS England and the breast cancer community to make trastuzumab deruxtecan available earlier in the treatment pathway of eligible patients in England with progressed HER2 positive metastatic breast cancer. Entry into the Cancer Drugs Fund is an important step in enabling timely access for patients whilst further evidence is gathered,” said Farhan Mughal, Director, Market Access and HEOR, Daiichi Sankyo UK.

“There remains a high level of unmet need in breast cancer and this approval represents an important step in our mission to bring new treatment options to UK patients earlier in the breast cancer pathway,” said Dr Oonagh McGill, Market Access Director, AstraZeneca UK.

Daiichi Sankyo and AstraZeneca UK will continue working in close partnership with NICE as additional data are collected throughout the managed access period. During this time, 600 eligible patients will be able to access trastuzumab deruxtecan via the CDF in advance of a decision from NICE on routine funding on the NHS.

The safety of trastuzumab deruxtecan, at the time of submission, was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of trastuzumab deruxtecan (5.4 mg/kg) in the DESTINY‑Breast03 trial.

The most common adverse reactions (frequency ≥20%), including laboratory abnormalities, nausea, decreased white blood cell count, decreased neutrophil count, increased aspartate aminotransferase, decreased haemoglobin, decreased lymphocyte count, increased alanine aminotransferase, decreased platelet count, fatigue, vomiting, increased blood alkaline phosphatase, alopecia, hypokalaemia, constipation, musculoskeletal pain, diarrhoea, decreased appetite, headache, respiratory infection, abdominal pain, increased blood bilirubin, and stomatitis.  Of the 27 events (10.5%) of interstitial lung disease (inflammation of the lung), 0.7% were recorded as CTCAE grade 3 events. No grade 4 or grade 5 ILD or pneumonitis events were adjudicated as drug-related.[6]

For further information about trastuzumab deruxtecan, such as the licensed indication and full safety profile, please refer to the summary of product characteristics.

Source: AstraZeneca