ASCO 2024: Targeted Triplet for Leptomeningeal Metastasis in HER2-Positive Breast Cancer

Treatment with the HER2-targeted tyrosine kinase inhibitor tucatinib plus trastuzumab and capecitabine demonstrated clinically meaningful benefit, including objective responses, extended survival, and improvements in symptoms and quality of life, in patients with newly diagnosed leptomeningeal metastases from HER2-positive breast cancer, according to Barbara Jane O’Brien, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. These findings from an additional analysis of the phase II TBCRC049 trial, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 2018), support the trend toward using systemic therapy as an initial approach in this clinical context.

“The combination of tucatinib, trastuzumab, and capecitabine is approved for patients with metastatic HER2-positive breast cancer, with or without brain metastases, who have received at least one prior HER2-based regimen in the metastatic setting,” the investigators remarked. “Patients with leptomeningeal metastases were excluded from the HER2CLIMB trial.”

Enrollment was planned for 30 patients; however, it closed at 17 patients following the U.S. Food and Drug Administration (FDA) approval of tucatinib in April 2020. In 21-day cycles, the population was treated with oral tucatinib, oral capecitabine, and intravenous trastuzumab. A total of 88% and 47% of patients were symptomatic and had abnormal cerebrospinal fluid cytology, respectively.

Of the 13 response-evaluable patients, 5 (38%) achieved a leptomeningeal metastasis objective response, and all (100%) achieved clinical benefit. More than half of the evaluable patients with target neurologic deficits at baseline (n = 7 of 12; 58%) seemed to experience an improvement in deficits. The entire study population completed at least 75% of the Linear Analog Scale Assessment (LASA) and MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) questionnaires at prespecified timepoints. The mean improvement in the LASA score was 13.5, suggesting improved quality of life. Improved symptom burden was indicated by a mean improvement in the MDASI-BT score of 32.0 points.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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