HER2-positive Breast Cancer: A Breakthrough Systemic Treatment for Brain Metastasis

In recent years, the treatment of HER2-positive breast cancer has evolved tremendously. Among its manifestations is a high likelihood of brain metastasis, which traditionally posed significant challenges due to limited effective therapies and poor prognosis upon relapse in this phase. However, an update on the Destiny 12 trial offers encouraging news for patients with active HER2-positive breast cancer that has spread to the brain (also known as ‘brain metastasis’).

Background

HER2 is a protein overexpressed in approximately one out of every five cases of invasive breast cancer, making this subtype among the most aggressive forms. When present with active or recurrent brain metastasis, it becomes even more concerning due to historically limited treatment options and poor survival rates post-relapse. This trial focused specifically on patients diagnosed with HER2-positive disease exhibiting such symptoms – a particularly high risk group given the propensity for these tumors to relocate within their own body, including the brain.

Destiny 12 Trial

The Destiny trial aimed at evaluating an innovative treatment approach using Trastuzumab Emtansine (T-DXd), a drug conjugate with trastuzumab, and deruxtecan. The study’s primary endpoint was to assess the response rate in patients receiving this systemic therapy without concurrent radiation treatments for their brain lesions – an approach unprecedented at that time.

In remarkable findings, a significant majority of participants experienced substantial tumor shrinkage or complete responses (CR) following treatment with T-DXd and deruxtecan alone—over 70% responded positively without the need for radiation therapy in most cases.

Results

The trial reported durable tumor shrinkage or CR rates persisting up to around 16-18 months, with some patients maintaining responses longer. This is noteworthy as the systemic approach eliminated the need for radiation therapy in many cases – a standard yet invasive treatment method that comes with risks and side effects.

Implications

These results suggest patients, regardless of whether their tumors express estrogen receptors (ER) or not, can benefit from this non-invasive systemic therapy approach. It offers a promising alternative for HER2+ breast cancer treatment with brain metastasis and presents the potential to substantially improve quality of life without requiring radiation—an invasive yet often necessary component in past treatments.