Study Reveals Encouraging Results in HER2+ Breast Cancer With Brain Mets

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Barbara O’Brien, MD, discussed findings and implications from the phase 2 TBCRC049 study evaluating the combination of tucatinib, trastuzumab, and capecitabine in HER2-positive breast cancer with leptomeningeal metastasis.

3D illustration of brain anatomy: © PIC4U - stock.adobe.com

3D illustration of brain anatomy: © PIC4U - stock.adobe.com

The phase 2 TBCRC049 study (NCT03501979) investigating the combination of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine for the treatment of patients with HER2-positive breast cancer and leptomeningeal metastasis showed promising results.

Leptomeningeal metastasis is a serious condition where cancer cells spread to the brain and spinal cord and is associated with poorer prognosis.

The study found that patients experienced improvements in symptoms, quality of life, and overall survival. Many patients also achieved objective responses.

These findings suggest that this drug regimen could be a valuable treatment option for patients with HER2-positive breast cancer and leptomeningeal metastasis. Further research is needed to confirm these results and explore potential benefits in other patient populations.

In an interview with Targeted OncologyTM, Barbara O’Brien, MD, associate professor of neuro-oncology at MD Anderson Cancer Center and primary investigator of the study, discussed the findings and implications from TBCRC049.

Targeted Oncology: What are the unmet needs in the patient population this study focused on?

Barbara O'Brien, MD

Barbara O'Brien, MD

O’Brien: The study population is patients with leptomeningeal metastasis. Leptomeningeal metastasis is associated with neurologic decline and a very poor prognosis, and we have no standard treatment options. We have a great need for clinical trials and better options for our patients.

What was the study evaluating? What were your goals?

Our study evaluated the HER2-directed [tyrosine kinase inhibitor] tucatinib, trastuzumab, and capecitabine in patients with HER2-positive breast cancer and leptomeningeal metastasis that was newly diagnosed. Our primary end point was overall survival. We were also looking at [cerebrospinal fluid (CSF)], pharmacokinetics, as well as response assessment, symptoms, and quality of life.

Could you summarize your findings?

The study initially enrolled robustly, but no longer enrolled patients receive tucatinib when it became FDA approved. So, the 17 patients that were involved, we found a median overall survival of 10 months, which compared favorably to the historic control of 4.4 months. This was previously reported. Now, we are reporting on our response data, and we found that over one-third of patients achieved a composite leptomeningeal response. The majority of patients had improvement of their symptoms that were present at baseline.

What would your takeaways be for clinicians based on these findings?

It is a small study, but the findings do support the option of the tucatinib regimen in patients who have leptomeningeal metastasis from HER2-positive breast cancer.

What do you see as some of the next steps, either with this agent or with this line of research in leptomeningeal disease?

This regimen offers a glimmer of hope, but we would like to do more for our patients in terms of the durability of response. Some considerations include combining tucatinib with other systemic agents or intrathecal agents and also further consideration of the sequencing of this drug regimen with other options for patients with leptomeningeal metastasis.

How can trials be better designed to assess patients with leptomeningeal metastasis?

Historically, patients with brain metastasis and, by extension, leptomeningeal metastasis have been excluded from breast cancer trials, in part because this is a unique subset of patients with breast cancer and there are certain implications in terms of their needs and the response to therapy and the overall survival. But I think it is important that, moving forward, we do include patients with brain metastases such as was done the pivotal HER2CLIMB study [NCT02614794]. Hopefully, we also have cohorts available for patients with leptomeningeal metastasis and open trials specifically for patients with leptomeningeal metastasis.

REFERENCE:
O’Brien B, Murthy R, Berry A, et al. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. J Clin Oncol. 2024;42(suppl 16): abstr 2018. doi:10.1200/JCO.2024.42.16_suppl.2018
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