Dr Lobbous on Tucatinib Plus Trastuzumab/Capecitabine in HER2+ Breast Cancer Leptomeningeal Metastases

Mina Lobbous, MD, MPH, assistant professor of neurology, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, member, Neuro-Oncology Staff, Brain Tumor Center, Cleveland Clinic Foundation, discusses data from phase 2 TBCRC049 trial (NCT03501979) investigating combination therapy consisting of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine in patients with leptomeningeal metastases from HER2-positive breast cancer.

Study investigators initially planned on enrolling 30 patients with HER2-positive breast cancer and newly diagnosed leptomeningeal metastases, Lobbous says. However, enrollment was stopped at 17 patients after the FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received 1 or more prior anti-HER2–based regimens in the metastatic setting in April 2020.

Findings from the study presented at the 2024 ASCO Annual Meeting showed that the 17 treated patients experienced extended overall survival (OS), improvements in patient-reported outcomes, and an increase in neurological function, Lobbous continues. Data demonstrated that among 13 response-evaluable patients, all achieved a complete response, partial response, or stable disease. Notably, 5 patients (58%) experienced a leptomeningeal metastasis objective response per composite criteria.

Among the 17 patients enrolled in the study, 4 were alive at data cutoff. The median OS was approximately 10 months, according to Lobbous. Additionally, MD Anderson Symptom Inventory Brain Tumor and Linear Analog Scale Assessment of Quality of Life scores both improved over time during treatment.

In 12 patients with up to 4 neurological deficits stemming from leptomeningeal metastases at baseline, 7 patients (58%) experienced improvements in these deficits. The deficits remained stable in the 5 patients who did not experience improvements.

Lobbous concludes by noting that these data indicate that the combination of tucatinib, trastuzumab, and capecitabine is effective in the treatment of patients with newly diagnosed leptomeningeal metastases stemming from HER2-positive breast cancer.