Tucatinib plus trastuzumab and capecitabine increased survival of patients with HER2-positive breast cancer spread to the brain

This study looked at treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and brain metastases (BM) with tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine (Xeloda). This study found that this treatment reduces the risk of cancer worsening in these patients. 

Up to half of the individuals with HER2-positive breast cancer will go on to develop BMs over the progression of their disease. Standard treatment for BMs includes surgery, radiosurgery, and/or whole-brain radiation. Unfortunately, the rate of progression of BMs is high. Guidelines state that treatment with systemic (that goes through the bloodstream and affects the entire body) therapies should continue after local therapy until disease progression. 

Cyclin-dependent kinases (CDKs) are molecules involved in cell multiplication and growth. Tucatinib is a targeted therapy that blocks CDKs. Trastuzumab is also a targeted therapy that is used in HER2-positive cancer treatment. Capecitabine is a chemotherapy agent. Tucatinib was FDA approved in April 2020 for use in patients with advanced HER2-positive breast cancer in combination with trastuzumab and capecitabine. However, the effectiveness of this combination on the progression of BMs is still unknown. 

This study included 291 patients with HER2-positive breast cancer and BMs. Patients were randomly assigned to 2 groups. Group 1 received tucatinib combined with trastuzumab and capecitabine (198 patients). Group 2 received a placebo combined with trastuzumab and capecitabine (93 patients). Patients had brain MRI scans before treatment, every 6 weeks for 24 weeks and every 9 weeks thereafter to assess BM.

The 1-year survival rate without the progression of BMs was 40.2% in group 1 compared to 0% in group 2. The estimated 1-year survival rate was 70.1% in group 1 compared to 46.7% in group 2. The risk of progression or death was 68% lower in group 1. 

The average survival period without the progression of BMs was 9.9 months. This was compared to 4.2 months in group 2. The average overall survival in the tucatinib group was 18.1 months versus 12.0 months in the placebo group. 

There were 75 patients who had active BMs that could be measured at the beginning of the study. The overall response rate in the brain was 47.3% for group 1 compared to 20% for group 2. 

This study concluded that tucatinib added to trastuzumab and capecitabine treatment significantly improved tumor response and survival of patients with HER2-positive breast cancer and BMs. 

The study was supported by Seattle Genetics, the manufacturer of tucatinib.