ASCO20: Tucatinib Combination Therapy for Breast Cancer With Brain Metastases
Posted: Wednesday, June 24, 2020
A subset analysis of the HER2CLIMB trial conducted by Nancy U. Lin, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues revealed treatment with the HER2 kinase inhibitor tucatinib in combination with trastuzumab and capecitabine may be linked to a decreased risk of intracranial disease progression and death in patients with HER2-positive metastatic breast cancer. The findings were presented during the ASCO20 Virtual Scientific Program (Abstract 1005) and published in the Journal of Clinical Oncology.
“[The trial demonstrated] statistically significant and clinically meaningful improvements in progression-free survival and overall survival,” Dr. Lin stated in an ASCO press release. “Tucatinib is the first tyrosine kinase inhibitor to demonstrate prolongation of overall survival in patients with HER2-positive metastatic breast cancer with brain metastases in a randomized, controlled trial.”
Of the 612 patients enrolled in the HER2CLIMB trial, the analysis focused on 291 patients with HER2-positive metastatic breast cancer and MRI-confirmed brain metastases. Each patient was treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) prior to the study. In a 2:1 allocation ratio, they were randomly assigned to receive either tucatinib or a placebo in addition to trastuzumab and capecitabine.
The median central nervous system progression-free survival for the experimental and control group was 9.9 months versus 4.2 months, respectively. Additionally, the experimental treatment reduced the risk of death by 42% (P = .005) and improved overall survival (median, 18.1 vs. 12.0 months). The intracranial confirmed objective response rate was 47.3% in the experimental group and 20.0% in the control group. The investigators also reported a longer confirmed intracranial duration of response (median, 6.8 vs. 3.0 months) and progression-free survival from randomization (median, 15.9 vs. 9.7 months) in the experimental group than the control group. The risk of second disease progression or death was reduced by 67% in patients with isolated brain progression who continued the experimental therapy after local treatment.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
