Exciting trial results with trastuzumab deruxtecan (Enhertu)

Latest results from clinical trials with trastuzumab deruxtecan (brand name: Enhertu) have shown significant benefits for two groups of patients with advanced breast cancer: those with high levels of HER2 (HER2 positive), and also those with low levels of HER2 (HER2-low, a subset of HER2 negative breast cancers).

This drug has two components: trastuzumab allows it to home in on HER2 receptors on breast cancer cells, and then the deruxtecan component gets to work killing the cells.

Trastuzumab will already be familiar to those with HER2 positive breast cancer – on its own it is the drug Herceptin, which is routinely used to treat both early and advanced cancers of this sub-type.

When Herceptin and taxanes stop working in those with advanced HER2 positive breast cancer, the next line of treatment usually recommended is Kadcyla. However, recent results from the DESTINY-Breast03 trial, which compared Kadcyla with Enhertu, showed that the newer drug gave better results. While Kadcyla gave 6.8 months progression free survival, Enhertu gave 25 months. Even those with brain metastases benefited.

Metavivors petitioned the New Zealand government for Kadcyla in 2018. Pharmac funded it for HER2 positive metastatic breast cancer in 2019. The new results from DESTINY-Breast03 strongly suggest that Enhertu should also be added to the New Zealand oncologist’s toolkit. BCAC has contacted NZ supplier Astra Zeneca who have said that they plan to apply to Medsafe for registration and Pharmac for funding, and to set up an interim patient-access programme for Enhertu.

A second trial with Enhertu, DESTINY-Breast04, has shown improvements in progression-free and overall survival in those with HER2-low advanced breast cancer. Breast cancer tumours expressing low levels of HER2 are usually classified as ‘HER2 negative’ and it was thought that drugs targeting HER2 would not be useful for these patients. These results turn that idea on its head.

Patients enrolled in the DESTINY-Breast04 trial were all HER2-low and had already received 1 or 2 lines of chemotherapy for their metastatic disease. Any whose breast cancer was also hormone receptor positive had to have got to the point where hormone therapy no longer worked. Those receiving Enhertu had a median improvement in progression-free survival of 4.8 months and 6.6 months in overall survival, compared to those receiving standard chemotherapy.

The researchers heralded this as a new standard of care for patients with HER2-low metastatic breast cancer. The DESTINY-Breast04 findings also justify a shift in the way pathology laboratories report HER2 results, with ‘HER2-low’ as a new and useful category. It is estimated that about 50% of breast cancer patients could be classified as HER2-low. BCAC has been told that New Zealand pathology labs are capable of reporting HER2-low status but need clinicians to ask for it. When Enhertu becomes available here, that is likely to happen.

7 July 2022

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