Abstract 328TiP
Background
A combination of a taxane, trastuzumab, and pertuzumab (THP) is the standard-of-care (SOC) 1L treatment for patients (pts) with HER2+ mBC; THP demonstrated median progression-free survival (mPFS) of 18.7 mo and overall survival (OS) of 56.5 mo (Swain et al. N Engl J Med. 2015;372:724-734). However, pts eventually develop resistance to treatment. Novel treatment options are necessary in order to delay the emergence of resistance and provide better clinical outcomes, improve quality of life (QOL), and prolong survival in the 1L setting. T-DXd has demonstrated efficacy in pts with heavily pretreated HER2+ mBC, with an objective response rate (ORR) of 61.4%, duration of response (DOR) of 20.8 mo, and mPFS of 19.4 mo (Modi et al. Cancer Res. 2021. Abstract PD3-06). Data from DESTINY-Breast01 supported global approvals of T-DXd in HER2+ mBC. Here we describe a phase 3 trial evaluating the efficacy and safety of T-DXd ± pertuzumab compared with THP in the 1L treatment of HER2+ mBC.
Trial design
DESTINY-Breast09 (NCT04784715) is a global, multicenter, randomized, phase 3 trial assessing the efficacy and safety of T-DXd with or without pertuzumab compared with SOC THP as 1L treatment in pts with HER2+ (IHC 3+ or ISH+ assessed locally per ASCO-CAP guidelines and centrally confirmed) advanced or mBC. This study consists of 3 treatment arms: arm A (T-DXd + placebo), arm B (T-DXd + pertuzumab), and arm C (THP). Randomization is 1:1:1 and pts will be stratified by prior treatment status (de novo vs recurrent), hormone receptor status (positive vs negative), and PIK3CA mutation status (detected vs not detected). Pts (N≈1134) must have had no prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). The primary endpoint is PFS by blinded independent central review. Secondary endpoints include PFS by investigator assessment, OS, ORR, DOR, PFS2, health-related quality of life (QOL), pharmacokinetics, immunogenicity, and safety.
Clinical trial identification
NCT04784715.
Editorial acknowledgement
Medical editorial assistance was provided by ArticulateScience LLC, and funded by AstraZeneca Pharmaceuticals LP.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
S.M. Tolaney: Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Other, honorarium for steering committee participation and consultant/advisory board: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Merck; Financial Interests, Institutional, Principal Investigator: Nektar; Financial Interests, Personal, Other, honorarium for consultant/advisory board; travel expense reimbursement for ad board: Nektar; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Pfizer; Financial Interests, Institutional, Principal Investigator: Genentech/Roche; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Genentech/Roche; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Eisai; Financial Interests, Institutional, Principal Investigator: Nanostring; Financial Interests, Personal, Other, honorarium for consultant/advisory board: Nanostring; Financial Interests, Personal, Advisory Board, honorarium for consultant/advisory board: Puma; Financial Interests, Institutional, Principal Investigator: Cyclacel; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Personal, Advisory Board, Honorarium for advisory board: Sanofi; Financial Interests, Personal, Advisory Board, Honorarium: Celldex; Financial Interests, Institutional, Principal Investigator: Odonate; Financial Interests, Personal, Advisory Board, honorarium for consultant/advisory board: Odonate; Financial Interests, Personal, Other, Honorarium for consulting: Seattle Genetics; Financial Interests, Personal, Advisory Board, Honorarium for Advisory Board: Silverback Therapeutics; Financial Interests, Personal, Advisory Board, Honorarium for Advisory Board: G1 Therapeutics; Financial Interests, Personal, Other, Honorarium for consulting: AbbVie; Financial Interests, Personal, Other, Honorarium for consulting: Athenex; Financial Interests, Personal, Advisory Board, Honorarium for ad board: OncoPep; Financial Interests, Personal, Advisory Board, Honorarium for ad board: Kyowa Kirin Pharmaceuticals; Financial Interests, Personal, Advisory Board, Honorarium for ad board: Daiichi Sankyo; Financial Interests, Personal, Other, Honorarium for consulting: CytomX; Financial Interests, Personal, Advisory Board, Honorarium for ad board: Samsung Bioepsis Inc.; Financial Interests, Personal, Advisory Board, Honorarium for ad board: Certara; Financial Interests, Personal, Advisory Board, Honorarium for ad board: Mersana Therapeutics; Financial Interests, Institutional, Advisory Role, Honorarium for consultant/advisory board: Immunomedics/Gilead; Financial Interests, Personal, Invited Speaker, Honorarium for consultant/advisory board: Immunomedics/Gilead. R. Barroso-Sousa: Financial Interests, Personal, Other, Sponsor of the study: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting fees: Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting fees: MSD; Financial Interests, Personal, Advisory Role, Consulting fees: Roche; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BARD ACESS; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Eli Lilly; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: LIBBS; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Daiichi Sankyo; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Roche; Financial Interests, Personal, Other, Speaker fee: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Speaker fee: Novartis; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Novartis; Non-Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant, Contracted research: Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Merck; Non-Financial Interests, Personal, Other, Medical writing support by Daniel Clyde of Health Interactions, was funded by F. Hoffmann-La Roche: F. Hoffmann-La Roche Ltd. M. Rimawi: Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: ORINOVE FOSUN; Financial Interests, Personal, Other, Consulting fees: Genentech; Financial Interests, Personal, Other, Consulting fees: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting fees: Seattle Genetics; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Macrogenics; Financial Interests, Personal, Funding, honoraria: Novartis. C. Saura Manich: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Consulting or Advisory Role: Celgene; Financial Interests, Personal, Other, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting or Advisory Role: Eisai; Financial Interests, Personal, Other, Consulting or Advisory Role: Genomic Health; Financial Interests, Personal, Other, Consulting or Advisory Role: Novartis; Financial Interests, Personal, Other, Consulting or Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Consulting or Advisory Role: Synthon; Financial Interests, Personal, Other, Consulting or Advisory Role: Piqur; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or Advisory Role: Philips HealthWorks; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role: Exact Sciences International SÀrl; Financial Interests, Personal, Other, Consulting or Advisory Role: Puma Biotechnology; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: prIME Oncology; Financial Interests, Personal, Other, Consulting or Advisory Role: Odonate Therapeutics; Financial Interests, Personal, Other, Consulting or Advisory Role: Pfizer/EMD Serono; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genomic Health; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Piqur. A. Schneeweiss: Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Celgene; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer. M. Toi: Financial Interests, Personal and Institutional, Research Grant: Chugai; Financial Interests, Personal and Institutional, Research Grant: Takeda; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Kyowa-Kirin; Financial Interests, Personal and Institutional, Research Grant: Taiho; Financial Interests, Personal and Institutional, Research Grant: JBCRG association; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Astellas; Financial Interests, Personal and Institutional, Research Grant: Shimadzu; Financial Interests, Personal and Institutional, Research Grant: Yakult; Financial Interests, Personal and Institutional, Research Grant: Nippon Kayaku; Financial Interests, Personal and Institutional, Research Grant: Luxonus; Financial Interests, Personal and Institutional, Research Grant: Shionogi; Financial Interests, Personal and Institutional, Research Grant: GL Science; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Exact Science; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Shimadzu; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Advisory Board: Kyowa-Kirin; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Konica Minolta; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Athenex Oncology; Financial Interests, Personal, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Advisory Board: Luxonus; Financial Interests, Personal, Advisory Board: Kansai Medical Net; Non-Financial Interests, Personal, Member of the Board of Directors: JBCRG; Non-Financial Interests, Personal, Member of the Board of Directors: OOTR; Non-Financial Interests, Personal, Member of the Board of Directors: KBCRN. T. Yu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Shetty: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P. Herbolsheimer: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Loibl: Financial Interests, Institutional, Other, grants and honorarium: AbbVie; Financial Interests, Institutional, Other, grants and honorarium: Amgen; Financial Interests, Institutional, Other, grants and honorarium: AstraZeneca; Financial Interests, Institutional, Other, grants and honorarium: Celgene; Financial Interests, Institutional, Other, grants and honorarium: Daiichi Sankyo; Financial Interests, Institutional, Other, grants and honorarium: Novartis; Financial Interests, Institutional, Other, grants and honorarium: Pfizer; Financial Interests, Institutional, Other, grants and honorarium: Roche; Financial Interests, Institutional, Other, grants and honorarium: Seattle Genetics; Financial Interests, Institutional, Other, honorarium: Bayer; Financial Interests, Institutional, Other, honorarium: BMS; Financial Interests, Institutional, Other, honorarium: Eirgenix; Financial Interests, Institutional, Other, honorarium: GSK; Financial Interests, Institutional, Other, honorarium: Ipsen; Financial Interests, Institutional, Other, honorarium: Lilly; Financial Interests, Institutional, Other, honorarium: Merck; Financial Interests, Institutional, Other, honorarium: Pierre Fabre; Financial Interests, Institutional, Other, honorarium: PriME/Medscape; Financial Interests, Institutional, Other, honorarium: Puma; Financial Interests, Institutional, Other, honorarium: Samsung; Financial Interests, Institutional, Research Grant: Cepheid; Financial Interests, Institutional, Research Grant: Immunomedics/Gilead; Financial Interests, Institutional, Research Grant: Vifor; Non-Financial Interests, Institutional, Other, medical writing: Amgen; Non-Financial Interests, Institutional, Other, medical writing: AstraZeneca; Non-Financial Interests, Institutional, Other, medical writing: BMS; Non-Financial Interests, Institutional, Other, medical writing: Celgene; Non-Financial Interests, Institutional, Other, medical writing: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, medical writing: Novartis; Non-Financial Interests, Institutional, Other, medical writing: Roche; Financial Interests, Institutional, Other, patents pending: EP21152186.9, EP18209672.7 and EP15702464.7; Financial Interests, Institutional, Licensing Fees: VM Scope GmbH; Financial Interests, Personal, Other, personal fee: Chugai; Financial Interests, Personal, Full or part-time Employment: GBG Forschungs GmbH; Non-Financial Interests, Personal, Other, Steering Committees: Immunomedics/Gilead; Non-Financial Interests, Personal, Other, Steering Committees: Novartis; Non-Financial Interests, Personal, Other, Steering Committees: Pfizer; Non-Financial Interests, Personal, Other, Steering Committees: Roche; Non-Financial Interests, Personal, Other, Steering Committees: Seattle Genetics; Non-Financial Interests, Personal, Member of the Board of Directors: BIG; Non-Financial Interests, Personal, Member: PI Aphinity; Financial Interests, Personal, Member, German Gynaeological Oncology Society: AGO; Financial Interests, Personal, Member: ASCO; Financial Interests, Personal, Member, German Cancer Society: DKG; Financial Interests, Personal, Member, Member, Chair ESMO Breast & Steering Committee: ESMO. All other authors have declared no conflicts of interest.