SABCS 2019: Tucatinib-Based Therapy for HER2-Positive Metastatic Breast Cancer
Posted: Thursday, December 12, 2019
Adding the tyrosine kinase inhibitor tucatinib to trastuzumab and capecitabine for patients with advanced HER2-positive metastatic breast cancer significantly improved progression-free and overall survival. These findings from the HER2CLIMB trial were presented during the 2019 San Antonio Breast Cancer Symposium (SABCS; Abstract GS1-01) and simultaneously published in The New England Journal of Medicine. Rashmi Krishna Murthy, MD, of MD Anderson Cancer Center, Houston, and colleagues noted that both those with and without metastasis obtained benefit. Based on these results, there are plans to submit a new drug application to the U.S. Food and Drug Administration in early 2020.
“This trial verified that tucatinib is both a safe and effective treatment,” said Dr. Murthy in an MD Anderson press release. “These results are unprecedented for late-line therapy in advanced breast cancer and are a major advance for patients who have [a] significant unmet medical need. Tucatinib in combination with trastuzumab and capecitabine should be the new standard of care for patients pretreated with multiple anti-HER2 agents including patients with brain metastasis.”
A total of 612 patients with locally advanced or metastatic HER2-positive breast cancer were enrolled in the double-blind, international, multicenter study. Prior to enrollment, they were treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). The patients were randomly assigned to receive either tucatinib (300 mg twice daily) or placebo, in addition to capecitabine (1,000 mg/m2 twice daily on days 1–14 of each 21-day cycle) and trastuzumab (6 mg/kg once every 21 days). Nearly half of the study patients had brain metastasis at baseline.
Compared with trastuzumab and capecitabine alone, the tucatinib combination therapy reduced the risk of death by 46%. It also prolonged overall survival, reduced the risk of death by 34%, and improved progression-free survival by 52% among patients with brain metastasis. The overall response rate with the tucatinib combination was 41%, compared with 23% with the standard of care.
Disclosure: The study authors’ disclosure information can be found at abstractsonline.com.