Breast cancer brain metastases treated with tucatinib

By Edward Susman

5 Jun 2020

Treatment with the targeted agent tucatinib appears to reduce the risk of death or the risk of progression of brain metastases in patients diagnosed with advanced breast cancer when compared with patients just treated with trastuzumab and capecitabine, researchers reported at the ASCO 2020 virtual meeting.

The risk of experiencing the composite primary endpoint was reduced by 68% [HR 0.32 (95%CI 0.22-0.48, P<0.0001)], reported Dr Nancy Lin, associate professor of medicine at Dana-Farber Cancer Institute/Harvard Medical School, Boston.

Patients who were treated with trastuzmab and capecitabine achieved a median overall survival of 12.0 months but that survival was increased to 18.1 months with addition of tucatinib (P=0.005), Dr Lin said. Trastuzumab is a small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

In her oral presentation, and in publication of her paper simultaneously in the Journal of Clinical Oncology, Dr Lin said that the median central nervous system progression-free survival was 9.9 months in the tucatinib-treated patients compared with 4.2 months among the patients getting trastuzmab and capecitabine (P=0.03).

In reporting the results of the HER2CLIMB trial which specifically studied intracranial lesions, Dr Lin  found that responses were observed in 47.3% of the patients on tucatinib compared with 20% of the patients on trastuzumab/capecitabine (P=0.03). In addition, at one year, 70% of patients randomised to tucatinib were alive compared to 47% of patients randomised to the placebo arm of the study.

In commenting on the results of HER2CLIMB, the designated discussant, Dr Aleix Prat, head of medical oncology at the Hospital Clinic of the University of Barcelona, Spain, said: “Overall these were very impressive results.” He noted that the last decade has shown major improvements in survival among breast cancer patients with advanced disease “But,” he said, “we still have work to do” and that particularly surrounds the need for treating brain metastases.

“The results in patients with central nervous system disease look very similar to the results in the general population of HER2CLIMB. In terms of response, it was 47% compared to 41% in the general population; in terms of median progression-free survival, it was 7.6 months compared to 7.8 months in the general population. And in terms of overall survival it was 18.1 months compared with 22 months in the general population,” Dr Prat said in his pre-recorded comments.

In her report, Dr Lin said: “Up to 50% of patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer will develop brain metastases during the course of their disease. Initial therapy for brain metastases typically consists of locally directed therapy with surgical resection, stereotactic radiosurgery, and/or whole-brain radiation therapy. Unfortunately, the rate of intracranial progression within six to 12 months with these therapies is high.”

In the subset of patients that comprised the current trial report, brain MRI was required every six weeks for the first 24 weeks and every nine weeks thereafter. Eligible patients did not require immediate local therapy for their CNS lesions. The median age was about 50 years; all the patients were ECOG performance status of 0-1. Forty percent of patients initially presented with de novo metastatic breast cancer. Dr Lin said 97% of the patients has co-existing extracranial disease; 70% of patients had received prior radiotherapy and 14%-16% had previously been treated with central nervous system directed surgery.

The study was funded by Seattle Genetics of Bothell, Washington.

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