Dr O’Brien on Tucatinib Plus Trastuzumab/Capecitabine for Leptomeningeal Metastases in HER2+ Breast Cancer

Barbara Jane O’Brien, MD, associate professor of neuro-oncology, Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and capecitabine for the treatment of leptomeningeal metastases in patients with HER2-positive breast cancer.

O’Brien and colleagues presented findings from the phase 2 TBCRC049 study (NCT03501979) at the 2024 ASCO Annual Meeting. When the study was launched, enrollment was initially planned for 30 patients; however, enrollment closed at 17 patients following the April 2020 FDA approval of this tucatinib-based combination for the treatment of patints with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, following at least 1 prior anti-HER2-based regimen in the metastatic setting.

All 17 patients enrolled had evidence of leptomeningeal metastases on MRI; notably, 82% of patients also had brain metastases, and 65% received prior treatment for brain metastases. Eighty-eight percent of patients were symptomatic from leptomeningeal metastases.

Findings showed the leptomeningeal metastases objective response rate was 38% in evaluable patients (n = 13), and all patients in this population experienced a response or stable disease. O’Brien also explains that the median overall survival was approximately 10 months, which compared favorably with the historical control of 4.4 months.

Furthermore, 7 of 12 evaluable patients with target deficits at baseline experienced improvement following treatment. In this population who had deficits due to leptomeningeal metastases at baseline, no patients experienced a worsening of symptoms.

O'Brien notes that these findings underscore the need for further research to confirm this combination’s benefits in the treatment of leptomeningeal metastases in larger cohorts. These findings support the trend toward using systemic therapy as an initial approach in patients with leptomeningeal metastases from HER2-positive breast cancer, she concludes.