Abstract 280P
Background
Brain metastases (BM) are frequently diagnosed in HER2-positive breast cancer (BC) and add to morbidity and mortality. Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate approved for the treatment of HER2-positive metastatic BC but has not been specifically investigated in the context of BM. Here, we present preliminary results of the prospective, single-centre, single-arm, phase II TUXEDO-1 trial investigating T-DXd in HER2-positive BC patients (pts) with active BM.
Methods
TUXEDO-1 enrols pts with HER2-positive BC and newly diagnosed BM or BM with radiological progression after prior local therapy, prior exposure to trastuzumab and pertuzumab, and no indication for immediate local therapy. The primary endpoint is intracranial response rate (RR) centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria. Secondary endpoints consist of extracranial RR, progression-free survival, overall survival, safety, and quality-of-life. Based on a Simon’s two-stage phase II design with RR under alternative hypothesis of >60% and under null hypothesis of <26%, six evaluable pts with 3 responses are required for the first stage and additional 9 pts for the second stage. The null hypothesis will be rejected with a type I error rate of 5% and a power of 80% if ≥7 responses are observed in the overall sample.
Results
By April 1st 2021, a total of 10 pts received at least one dose of T-DXd. Median age is 48.5 years, 60% received prior radiotherapy for BM, and 70% prior T-DM1. At a median follow-up of 3.5 months (range 1-8), 9 pts are still on treatment. T-DXd yielded an intracranial response in 5/6 pts (83.3%) enrolled in the first stage (3/4 progressing after prior local therapy); thus, the trial progressed to the second stage. Main toxicities in the overall sample consisted of grade 1/2 nausea, neutropenia, and fatigue. No case of interstitial lung disease was detected; one patient with pre-existing diabetes experienced a reversible symptomatic drop of left-ventricular ejection fraction.
Conclusions
Based on clinically relevant preliminary activity in HER2-positive BC pts with active BM, TUXEDO-1 met the criteria to move to the second stage.
Clinical trial identification
EudraCT 2020-000981-41; NCT04752059.
Editorial acknowledgement
Legal entity responsible for the study
Medical University of Vienna, Department of Medicine 1.
Funding
Daiichi Sankyo.
Disclosure
R. Bartsch: Financial Interests, Personal, Invited Speaker: Astra-Zeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated Trial: MSD. A.S. Berghoff: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Amgen; Financial Interests, Personal and Institutional, Other: AbbVie; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche. M. Marhold: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: Medmedia; Financial Interests, Personal and Institutional, Other: Amgen; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Daiichi; Financial Interests, Personal and Institutional, Other: Eisai. A.M. Starzer: Financial Interests, Personal and Institutional, Other: PharmaMar. A. Ilhan-Mutlu: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Personal and Institutional, Other: BMS; Financial Interests, Personal and Institutional, Other: Eli Lilly; Financial Interests, Personal and Institutional, Other: Daiichi; Financial Interests, Personal and Institutional, Other: Roche. C. Minichsdorfer: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Other: MSD; Financial Interests, Personal and Institutional, Other: Merck. T. Fuereder: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Accord; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Merck. C.F. Singer: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Tesaro; Financial Interests, Personal and Institutional, Other: AstraZenca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi. M. Preusser: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: GLG; Financial Interests, Personal, Advisory Board: CMC Contrast; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Munidpharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other: BMJ Jorunals; Financial Interests, Personal, Other: MedMedia; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Medahead; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Tocagen; Financial Interests, Personal, Invited Speaker: AdAstra; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Novocure; Financial Interests, Institutional, Funding: GSK; Financial Interests, Institutional, Funding: AbbVie. All other authors have declared no conflicts of interest.