The outcomes of trastuzumab emtansine in patients with brain metastasis from HER2-positive breast cancer

The study evaluated the effects of trastuzumab emtansine (T-DM1; Kadcyla) to treat patients with brain metastasis (BM) from HER2-positive metastatic breast cancer (mBC). The main finding was that T-DM1 was safe and effective in such patients.

HER-2 positive mBC cells have an excess of the HER-2 protein. Such cancers are more aggressive and difficult to treat. They often travel to the brain to cause BM. Patients with such conditions experienced improved survival when treated with T-DM1 in small clinical trials. T-DM1 is an antibody-based therapy. However, evidence from late-stage and large trials are lacking.

The clinical trial included 2002 patients with HER2-positive mBC. They were previously treated with chemotherapy and therapy targeting HER2. 398 patients had BM at the start of the trial (baseline). BMs were larger and measurable in millimeters in 126 patients. All patients received T-DM1 into the vein every 3 weeks. On average, this continued for 4.9 months in patients with BM at the start of the trial and 5.8 months in those without. Patients were followed-up for 20.6 months on average.

Among 126 patients with measurable BM, 3 achieved a complete response (CR). CR means the absence of all clinical cancer symptoms. 24 faced partial response (PR), meaning tumor shrinkage. Additionally, 27 patients’ cancer did not progress for more than 6 months.

Progression-free survival (PFS) refers to how long patients survive without cancer worsening. The average PFS was 5.5 months in patients with and 7.7 months in those without baseline BM. The average overall survival (OS) was 18.9 months in patients with baseline BM and 30.0 months in those without. 

269 patients developed new brain lesions during therapy. This included 28.9% of the patients with baseline BM and 9.6% of those without baseline BM. T-DM1 treatment continued for such patients whose brain lesions were surgically removable or manageable by radiotherapy.

Unexpected medical events occurred similarly among patients with or without baseline BM. Side effects in the nervous system happened more commonly in patients with baseline BM (52.3% vs 43.7%).

The authors concluded that T-DM1 showed good safety and effectiveness in patients with HER2-positive mBC and BM.

This trial is currently ongoing. The study is a post-hoc analysis which was not pre-planned. It was decided only after the data were obtained. Also, the number of patients was small and there was no comparison treatment.