260P Antitumor activity of trastuzumab deruxtecan (T-DXd) in patients with metastatic breast cancer (mBC) and brain metastases (BMs) from DAISY trial

Breast cancer constitutes the second most common cause of BMs with a higher prevalence in patients with triple-negative and HER2-positive mBC. T-DXd, an antibody-drug conjugate targeting HER2, has shown promising efficacy in patients with HER2-overexpressing mBC and treated asymptomatic BMs. We aimed to analyze the efficacy of T-DXd in patients with BMs and mBC according to HER2 status in patients from DAISY trial. DAISY is a phase II clinical trial (NCT04132960) that assessed T-DXd efficacy at the approved dose of 5.4 mg/kg every 3 weeks in mBC according to HER2-expression. Three cohorts of patients were included: cohort 1 (HER2-overexpressing: HER2 IHC3+ or HER2 IHC2+/ISH+), cohort 2 (HER2-low: IHC1+ or IHC2+/ISH-) and cohort 3 (HER2-null: IHC0+) with any hormone receptor status. Patients with treated and asymptomatic BMs, who did not receive any therapy to control BMs-related symptoms were eligible for enrollment. Patients with leptomeningeal disease were excluded. An MRI of the brain every 6 weeks the first year and then every 12 weeks was only required for patients with BMs at baseline. This analysis includes patients with BMs at baseline who received T-DXd. As of October 19, 2021, 24 pts with a history of BMs were included in the full analysis set, 12 (18%) in cohort 1, 10 (14%) in cohort 2, and 2 (5%) in cohort 3. 30% of patients from cohort 2 were hormone receptor-negative. 50% of patients in cohort 1 and 60% in cohort 2 received ≥ 5 prior lines of therapy. The best objective response rate (BOR), the clinical benefit rate (CBR) and the median progression-free survival (mPFS) are presented overall and per cohort in the table.Table: 260PResults of T-DXd activity in overall population and per cohortOverall n=24Cohort 1 n=12Cohort 2 n=10Cohort 3 n=2BOR % (n) [95% CI]62.5 (15/24) [40.6-81.2]91.7 (11/12) [61.5-99.8]30 (3/10) [6.7-65.2]50 (1/2) [1.3-98.7]CBR % (n) [95% CI]70.8 (17/24) [48.9; 87.4]91.7 (11/12) [61.5-99.8]50 (5/10) [18.7-81.3]50 (1/2) [1.3-98.7]mPFS (months) [95% CI]8.5 [4.4-12.2]13 [7.1-not reached]4.1 [2.3-11.7]NA [2.0-not reached] Open table in a new tab T-DXD showed meaningful antitumor activity in patients with mBC and history of BMs at baseline. Efficacy in Her2-low mBC is promising and warrants further investigation.