Survival Advantage Observed in HER2+Breast Cancer With Brain Metastasis

Nancy U. Lin, MD, associate professor of Medicine at Harvard Medical School, associate chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers, and director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, discusses the results from a substudy of HER2CLIMB looking at tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine in patients with HER2-positive breast cancer and brain metastases.

This subgroup was made up of about 300 patients who had brain metastases at baseline. Lin says the important distinction in these patients, in addition to the high proportion of the patients with brain metastases enrolled within the trial overall, is that 60% of them had active brain metastases. Most of the trials of breast cancer that included patients with brain metastases have only treated those with stable brain metastases. This study is the first registration trial of breast cancer to include patients with active brain metastases.

The results of this exploratory analysis showed this subset of patients in HER2CLIMB had a significant reduction by about two-thirds in time to central nervous system (CNS) progression or death. There was significant reduction in overall survival (OS) with a hazard ratio of 0.58, and this corresponded to a more than 6-month prolongation of median OS in this type of patient, according to Lin.

Among the subset of patients with measurable, active brain metastases at baseline, the CNS objective response rate was 47% versus 20% with trastuzumab and capecitabine alone. Lin thinks all of these data put together suggest that the triplet of tucatinib plus trastuzumab and capecitabine not only leads to response and PFS advantages for patients with brain metastases but also substantially improves OS.

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