Antibody–Drug Conjugates: Important New Steps for Breast Cancer, Including Brain Metastases

Antibody–drug conjugates (ADCs) are cancer treatments combining an antibody with a conjugate structure that carries a drug molecule to a targeted cancer cell. The antibody binds specifically to the cancer cell, delivering the drug directly and minimizing harm to surrounding healthy cells. This approach enables a more effective attack on cancer cells while reducing chemotherapy adverse effects.

Above, the general structure of antibody–drug conjugates is illustrated. Target antigens are usually found on cancer cell surfaces. The antibody binds to the cancer cell and then releases the cytotoxic (cell-killing) drug.

A Drug Class Changing the Outlook for Breast Cancer

New research into advanced or metastatic breast cancer offers encouraging findings supporting the use of these agents in broader patient groups.

Antibody–drug conjugates (ADCs) have expanded options for patients with unresectable advanced or metastatic breast cancer, offering new therapies when others are insufficient. The latest research presented at the ESMO 2024 Congress explored broader use of existing ADCs and the discovery of new ADCs targeting HER2 and HER3 to improve outcomes.

Note: three well-known ADC drugs approved for breast cancer are trastuzumab deruxtecan (Enhertu), trastuzumab emtansine (Kadcyla) and sacituzumab govitecan (Trodelvy).

Breakthrough Results for Patients with Brain Metastases

In HER2-positive metastatic breast cancer, patients commonly develop brain metastases, which generally make treatment difficult. Until now, radiotherapy had stood out as an unavoidable option for these patients, but its adverse effects could create substantial difficulties.

The latest results from the DESTINY-Breast12 clinical study showed substantial effectiveness of the ADC trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer and brain metastases.

Among the 263 participants with brain metastases, the 12-month progression-free survival (PFS) rate was 61.6%. Even among patients with active brain metastases, the rate was 60.1%. These results show that trastuzumab deruxtecan, whose ability to cross the blood–brain barrier had previously raised concerns, is also effective for patients with brain metastases. Patients can therefore achieve successful outcomes without needing local treatments such as radiotherapy,using systemic therapy alone.

A New HER3-Targeted Treatment: Patritumab Deruxtecan

Another important study presented at the congress focused on patritumab deruxtecan, a new ADC. It stands out as an effective option for patients with hormone receptor (HR)-positive and HER2-negative metastatic breast cancer. In particular, CDK-4/6 inhibitors and endocrine therapy had been followed by disease progression, and patients who had received one line of chemotherapy showed substantial responses to this new treatment.

Among the 99 study participants, the confirmed response rate was 53.5%, with a median of 9.4 months without disease progression.

Although the role of HER3 in cancer treatment has not been fully explored, these early results with patritumab deruxtecan suggest that targeting HER3 is a promising field. Some patients experienced fatigue, nausea, or diarrhea during treatment, but these adverse effects were described as manageable.

New Horizons in Cancer Treatment

ADCs are already among approved options for advanced breast cancer. Trastuzumab deruxtecan is used in HER2-positive and HER2-low breast cancer, while sacituzumab govitecan has been approved for heavily pretreated triple-negative and HR-positive/HER2-negative breast cancer. Scientists continue to investigate ADCs at earlier stages of cancer treatment. Their use in broader patient groups and management of adverse effects remain under study. Determining the sequence in which ADCs should be given is another important issue.

Further research in the coming years may enable ADCs to offer more personalized and effective cancer treatments. Scientists are working to understand their use across different patients and which biomarkers determine treatment response.

This research offers considerable hope, especially for treatment-resistant and difficult-to-treat breast cancers. It would not be wrong to say that ADCs are opening the door to a new era in cancer treatment.