New drug can have a promising effect in cancer patients with active brain metastases

An international clinical study led by the Medical University of Vienna shows that the drug patritumab deruxtecan (HER3-DXd) can have a promising effect in patients with active brain metastases of various tumor types. Patients with advanced disease benefited from treatment in both non-small cell lung cancer (NSCLC) and metastatic breast cancer, as shown in two simultaneous publications in The Lancet Oncology.

The study was conducted at centres in Austria and Spain, including the Clinical Division of Oncology, Department of Medicine I at MedUni Vienna and University Hospital Vienna. The investigations focused on the antibody-drug conjugate patritumab deruxtecan (HER3-DXd), which binds specifically to the cell surface protein HER3. Brain metastases are a common and difficult-to-treat problem in advanced cancer. Around one-third of patients with NSCLC and a significant proportion of patients with metastatic breast cancer develop metastases in the brain during the course of their disease. Existing treatment options are limited, especially when metastases progress after prior local treatment. Previous research by the Department of Oncology has already indicated that HER3 is particularly frequently expressed in brain metastases. This observation suggests that HER3 could be a promising therapeutic target.

Breast cancer: One quarter benefit from new therapy

In cohort 1 of the TUXEDO-3 study, 21 patients with metastatic breast cancer and active brain metastases were treated. Regardless of tumor subtype (hormone receptor-positive, HER2-positive, triple-negative), 23.8% achieved a response in the brain. Side effects were mostly manageable; serious adverse events occurred in 28.6% of patients, with no treatment-related deaths.

In about a quarter of patients with metastatic breast cancer and active brain metastases, HER3-DXd showed clear signs of activity in the brain. These were heavily pretreated patients, many of whom had no remaining effective treatment options - so a response rate of around 25% is a notable achievement. Just as important is the ability to maintain, or even improve, quality of life during therapy."

Rupert Bartsch, lead author, oncologist at the Clinical Division of Oncology, Department of Medicine I at MedUni Vienna and University Hospital Vienna

30 percent of NSCLC patients with active brain metastases respond

Cohort 2 of the TUXEDO-3 study investigated the efficacy of HER3-DXd in 20 patients with non-small cell lung cancer (NSCLC) and active brain metastases. An objective intracranial response was observed in six patients (30%), thereby meeting the predefined study endpoint. Remarkably, responses also occurred in patients without oncogenic driver mutations, suggesting that HER3-targeted antibody-drug conjugates may have broader therapeutic applicability beyond molecularly defined subgroups. According to Thorsten Füreder, first author of the publication and oncologist at the Division of Oncology, Department of Medicine I at the Medical University of Vienna and University Hospital Vienna, the study represents a significant step forward: "In TUXEDO-3, we evaluated for the first time the efficacy of a HER3-directed antibody-drug conjugate specifically in patients with advanced brain metastases from lung cancer. The observed intracranial responses constitute a meaningful advance for this particularly hard-to-treat population."

Potential targeted treatment option for brain metastases

"Both studies provide initial prospective evidence that HER3-DXd could be a novel, targeted treatment option for patients with brain metastases of lung and breast cancer," explains study leader Matthias Preusser, Head of the Clinical Division of Oncology at the Department of Medicine I at MedUni Vienna and University Hospital Vienna. "Our results suggest that HER3-DXd may be a potential treatment option not only for genetically defined subgroups, but also for broader patient groups with active brain metastases from breast and lung cancer."

HER3-DXd is not yet approved. Further larger studies are needed to confirm its clinical benefit.