Advance in breast cancer treatment

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Patients with advanced HER2-positive breast cancer very often develop brain metastases. When this happens, patients have low chances of surviving the next few years with existing therapies such as surgery and radiotherapy. Now an international team of researchers under the co-lead of Professor Nadia Harbeck, Director of the Breast Center at LMU University Hospital, has tested a new drug in a clinical trial. “With great results,” reports the oncologist. According to the findings to date, survival times increase substantially. The results of the trial have been published in the journal Nature Medicine.

Modern medicine divides breast cancer into different types according to tumorbiological characteristics. 50% of patients with advanced breast cancer and the tissue marker HER2 will suffer from brain metastases, which it has not been possible to treat successfully with drugs before now, as the blood-brain barrier often prevents active substances from penetrating into the brain. New drugs are therefore urgently required.

Precisely targeted antibody

One of these active substances is a so-called antibody-drug conjugate (ADC) called “trastuzumab deruxtecan.” Trastuzumab is an antibody which, once injected in the body, docks precisely to the HER2 protein. Its payload is the active ingredient deruxtecan, which kills cancer cells and is active in the tumor tissue and hardly anywhere else in the rest of the body. “This is why we can use this active ingredient in the first place,” explains Harbeck. “Otherwise, it would be much too toxic.”

To determine the benefit of the ADC for HER2-positive breast cancer, the LMU oncologist launched the DESTINY-Breast12 study as one of the two principal investigators. Over 500 patients with and without brain metastases, from 78 cancer centers in Western Europe, Japan, Australia, and the United States, took part in the trial. The results showed that on average, patients – even those with brain metastases – survived over 17 months without any progression of the cancer. More than 60 percent of patients survived 12 months without further tumor growth. The researchers detected regression of the brain metastases over 70 percent of participants. 90 percent of all patients were alive one year after the start of treatment. “These findings,” says Nadia Harbeck, “offer hope to patients with brain metastases in particular.” The drug is already approved for use in standard practice.

Overall, the cancer specialist attests that the ADC has “great potential for the treatment of breast cancer.” An example of this is a large trial, ADAPT HER2 IV, which has been running for the past year at the initiative of the West German study group. This worldwide unique trial is available for patients with early, non-metastasized HER2-positive breast cancer in Germany. Patients are given infusions of the ADC just four times before surgery, which considerably simplifies and shortens the therapy. In total, three ADCs are currently approved for breast cancer in Germany – “and I think,” says Harbeck, “there are many more to come.”

N. Harbeck et al.: Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial. Nature Medicine 2024