Tucatinib in combination with trastuzumab and capecitabine for HER2 positive metastatic breast cancer

This study aimed to investigate the safety and effectiveness of tucatinib in combination with trastuzumab and capecitabine in patients with HER2 positive metastatic breast cancer who have had disease progression with other treatments.  

This study concluded that this treatment combination was safe and effective in these patients.

Human epidermal growth factor receptor 2 (HER2) is a protein that promoted the growth of some breast cancers (BC). These are called HER2-positive (HER2+). Trastuzumab (Herceptin) and pertuzumab (Perjeta) are targeted therapy drugs used for HER2+ BC. Capecitabine (Xeloda) is a chemotherapy drug used to treat BC. 

Patients with HER2+ BC that has spread to distant organs (metastatic) who have disease progression despite multiple HER2-targeted treatments have limited treatment options. Tucatinib (Tukysa) is a type of targeted therapy known as a tyrosine kinase inhibitor (TKI). It targets HER2 tyrosine kinase. It is a new drug. 

 It was unknown if tucatinib in combination with trastuzumab and capecitabine would be safe and effective in patients with HER2+ metastatic BC.  

This study involved 612 patients with HER2+ metastatic BC. Patients had previously received trastuzumab, pertuzumab, or trastuzumab emtansine (Kadcycla) and had disease progression. Patients were then randomized to one of 2 groups. One group of patients received tucatinib in combination with trastuzumab and capecitabine. The other group received a placebo in combination with trastuzumab and capecitabine. Patients were followed up for an average of 14 months. 

Progression-free survival (PFS) at 1 year was 33.1% for the tucatinib group compared to 12.3% for the placebo group. The average duration of PFS for the tucatinib group was 7.8 months compared to 5.6 months for the placebo group. The risk of cancer worsening was 46% lower with tucatinib. 

The overall survival (OS) rate at 2 years was 44.9% for the tucatinib group compared to 26.6% for the placebo group. The average OS was 21.9 months for the tucatinib group compared to 17.4 months for the placebo group. Patients treated with tucatinib had a 34% lower risk of mortality. 

Among patients with brain metastases (cancer spread to the brain), PFS at 1 year was 24.9% for the tucatinib group compared to 0% for the placebo group. The average PFS was 7.6 months for the tucatinib group compared to 5.4 months for the placebo group.  

Common side effects for patients treated in the tucatinib group included diarrhea, nausea, fatigue, and vomiting. Diarrhea was more common in the tucatinib group compared to the placebo group. 

This study concluded that tucatinib combined with capecitabine and trastuzumab resulted in improved outcomes for patients with previously treated HER2+ metastatic BC.

Tucatinib has been approved by the FDA based on the results of this study. This study was funded by Seattle Genetics, the manufacturer of tucatinib.