Dr O'Brien on Breast Cancer Research in Patients With HER2+ Brain Metastases

Barbara Jane O’Brien, MD, associate professor, Neuro-Oncology, Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the importance of expanding clinical trial enrollment criteria to include patients with HER2-positive breast cancer with brain metastases.

Historically, patients with HER2-positive breast cancer who have brain metastases, including leptomeningeal metastases, have been excluded from many breast cancer clinical trials, O’Brien begins. These patients comprise a unique subgroup with needs, response patterns, and treatment outcomes that are distinct from those of patients without brain metastases, O’Brien says. However, in the future, patients with breast cancer brain metastases should be included in more clinical trials, O’Brien emphasizes. The phase 2 HER2CLIMB trial (NCT02614794) is a prime example of a study that successfully evaluated an effective treatment option for patients with disease involvement in the central nervous system, O’Brien notes. Findings from this study supported the 2020 FDA approval of tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine (Xeloda) for the treatment of pretreated adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases. Hopefully, future clinical trials in breast cancer will enroll cohorts of patients with leptomeningeal metastases or solely evaluate therapies in this patient population, O’Brien concludes.

At the 2024 ASCO Annual Meeting, O’Brien presented findings from the phase 2 TBCRC049 trial (NCT03501979), which investigated tucatinib plus trastuzumab and capecitabine in patients with HER2-positive breast cancer with leptomeningeal metastases. This trial enrolled 17 patients, all of whom had brain MRI evidence of leptomeningeal metastases. Eighty-two percent of patients also had brain metastases, and 65 of patients had received treatment for brain metastases. All 13 response-evaluable patients achieved clinical benefit with the regimen, and 5 achieved objective responses in their leptomeningeal metastases. Furthermore, 7 of 12 evaluable patients with target deficits at baseline had improved deficits with the treatment.