FDA Grants Breakthrough Therapy Designation to Tucatinib in Advanced HER2-Positive Breast Cancer
Posted: Monday, December 23, 2019
On December 18, Seattle Genetics announced that the U.S. Food and Drug Administration granted Breakthrough Therapy designation to tucatinib, in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). This designation is based on the results of the HER2CLIMB clinical trial, which were presented at the 2019 San Antonio Breast Cancer Symposium and simultaneously published in The New England Journal of Medicine. Tucatinib is an oral, small-molecule tyrosine kinase inhibitor that is highly selective for HER2.
The HER2CLIMB study compared tucatinib in combination with trastuzumab and capecitabine with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab, and T-DM1. Of the patients enrolled in the trial, 47% had brain metastases at the time of enrollment.
Based on the data of the first 480 patients enrolled in the trial, the addition of tucatinib improved progression-free survival compared with trastuzumab and capecitabine alone, with a 46% reduction in the risk of disease progression or death. The tucatinib arm experienced an improvement in overall survival, with a 34% reduction in the risk of death compared with the control arm. For patients with brain metastases at baseline, the tucatinib arm also demonstrated superior progression-free survival, with a 52% reduction in the risk of disease progression or death compared with the control arm.
The most common adverse events occurring in more than 20% of patients in the tucatinib arm versus the control arm included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Greater than or equal to grade 3 diarrhea was seen in 12.9% of the patients in the tucatinib arm versus 8.6% in the control arm.
