Abstract 260P
Background
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.
Methods
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.
Results
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: 260P
Results of T-DXd activity in overall population and per cohort
| Overall n=24 | Cohort 1 n=12 | Cohort 2 n=10 | Cohort 3 n=2 | |
| BOR % (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] |
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Pistilli: Non-Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Non-Financial Interests, Institutional, Advisory Board: MSD, Seattle Genetics, Lilly; Non-Financial Interests, Institutional, Funding: Daiichi Sankyo, AstraZeneca. F. André: Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, SeaGen; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, SeaGen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche. E. Deluche: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, FRESENIUS-KABI, Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, scientific events: Lilly, GSK; Financial Interests, Personal, Other, funding for conference travel: Astrazeneca-Daiichi, Roche, Amgen. V.C. Dieras: Financial Interests, Personal, Advisory Board: Roche, Novartis, Lilly, Pfizer, AstraZeneca, Abbvie, MSD, Daiichi Sankyo, Seagen, Gilead; Non-Financial Interests, Personal, Advisory Board: Eisai, Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.