FDA Approves Tucatinib in Combination Therapy for Metastatic Breast Cancer
Posted: Wednesday, April 22, 2020
On April 17, the U.S Food and Drug Administration (FDA) approved tucatinib (Tukysa) tablets to be used in combination with trastuzumab and capecitabine for the treatment of adults with advanced, unresectable, or metastatic HER2-positive breast cancer and patients with brain metastases who had received one or more prior anti–HER2-based regimens in the metastatic setting. Tucatinib is an oral, small-molecule tyrosine kinase inhibitor of the HER2 protein.
The FDA approval was based on the double-blind HER2CLIMB study results. The trial enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) separately or in a combination treatment. Of the 612 patients, 48% had a history of or presently had brain metastases. Patients were randomly selected to receive tucatinib in combination with trastuzumab and capecitabine or trastuzumab and capecitabine alone.
Patients who received the tucatinib-based combination showed a longer progression-free survival of 7.8 months versus 5.6 months for patients who received trastuzumab and capecitabine alone. The median overall survival in patients who received tucatinib was 21.9 months, compared with 17.4 months in patients who did not. For patients with brain metastases, the median progression-free survival for patients with brain metastases was 7.6 months in those who received tucatinib compared with 5.4 months who received placebo.
The most common adverse reactions occurring in 20% or more of patients were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Serious adverse reactions occurred in 26% of patients who received tucatinib. Serious adverse reactions included diarrhea (4%); vomiting (2.5%); as well as nausea, abdominal pain, and seizure (2% each). Adverse reactions leading to treatment discontinuation of tucatinib were hepatotoxicity (1.5%) and diarrhea (1%).
