Rashmi K. Murthy, MD, an assistant professor in the Department of Breast Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the pivotal HER2CLIMB trial, which evaluated the addition of tucatinib to trastuzumab (Herceptin) plus capecitabine in patients with HER2-positive metastatic breast cancer. The treatment options for this patient population are limited following progression on standard systemic treatments, and the disease remains incurable, says Murthy. Additionally, about half of the patients will develop brain metastases overtime during their disease course.
Tucatinib is an investigational oral tyrosine kinase inhibitor, which is highly selective for HER2 with minimal inhibition of EGFR. The agent may provide a more favorable toxicity profile, and in a phase Ib study, tucatinib plus trastuzumab and capecitabine was safe with encouraging antitumor activity in heavily pretreated patients, including those with brain metastases.
When tucatinib was added to the standard combination of trastuzumab and capecitabine, patients experienced an improvement in progression-free survival whether or not they had brain metastases. Murthy says there was a significant overall survival benefit in patients with brain metastases. This combination represents a major advance in the treatment of this patient population.
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