376O - Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study

Background

DESTINY-Breast04 (NCT03734029) assessed T-DXd vs TPC in pts with HER2-low mBC (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization−). At primary data cutoff (DCO; January 11, 2022), median overall survival (mOS) for the full analysis set (FAS = hormone receptor-positive [HR+] and hormone receptor-negative [HR−]) was 23.4 months (mo) for T-DXd vs 16.8 mo for TPC (hazard ratio, 0.64; P = 0.001), with 18.4 mo median follow-up (F/U). Here, we report results from a pre-planned further F/U (DCO, March 1, 2023).

Methods

Pts were randomly assigned 2:1 to T-DXd or TPC. At the updated DCO, analyses of OS (HR+ and FAS), progression-free survival (PFS) by investigator (HR+ and FAS), and safety were conducted.

Results

At DCO, median F/U was 32 mo. Median treatment duration was 8.2 mo (range, 0.2-39.1 mo) for T-DXd and 3.5 mo (range, 0.3-19.7 mo) for TPC. Efficacy results are shown in the table. Grade ≥3 treatment-emergent adverse events (TEAEs) were lower in T-DXd vs TPC (54.4% vs 67.4%). The most common TEAEs were gastrointestinal or hematological in nature; all-grade nausea (T-DXd: 76.0%; TPC: 30.2%) and vomiting (T-DXd: 40.7%; TPC: 13.4%) were most common for T-DXd and decreased neutrophil count (T-DXd: 22.1%; TPC: 36.0%) was most common for TPC. Exposure-adjusted incidence rates for any-grade TEAEs were 1.2 and 2.6 for the T-DXd vs TPC arm, respectively. No new adjudicated drug-related interstitial lung disease/pneumonitis events were reported with longer F/U (primary DCO: 45 pts [12.1%] for T-DXd; 1 pt [0.6%] for TPC).

Conclusions

Results from the 32-mo median F/U for DESTINY-Breast04 confirms the sustained clinically meaningful improvement for T-DXd vs TPC previously demonstrated in HER2-low mBC, regardless of HR status. Similar to the primary analysis, the overall safety profile was generally manageable with longer duration of treatment exposure. Table: 376O

Summary of efficacy results

m, median. Estimated and CI for OS rate at the specified time point are from Kaplan-Meier analysis.

Clinical trial identification

NCT03734029.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Lauren Carroll, MS, MPH, and Soniya Patel, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., and AstraZeneca.

Disclosure

S. Modi: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Genentech, AstraZeneca, Seagen, Macrogenics; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Genentech, AstraZeneca, Seagen. W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Coordinating PI: Roche, Daiichi Sankyo; Financial Interests, Local PI: Roche, Novartis, Daiichi Sankyo. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Steering Committee Member: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Novartis, Pfizer, Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Local PI: Lilly, Bayer, Behringer, Nihon Kayaku. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. J. Tsurutani: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Research Grant: Eisai, Eli Lilly, Ono. K. Zaman: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi, Lilly, Pierre Fabre, Gilead, MSD, Novartis, Seagen, Viatris; Financial Interests, Institutional, Funding, Translational study: Roche; Financial Interests, Institutional, Steering Committee Member: Pierre Fabre; Financial Interests, Institutional, Other, Member of the IDMC of an international trial: Roche; Financial Interests, Institutional, Steering Committee Member, Member of the Steering committee of an international study: Daiichi; Non-Financial Interests, Advisory Board: Swiss Group for Clinical Research Against Cancer (SAKK), Executive Committee of the MINDACT trial; Non-Financial Interests, Member, Representative of SAKK Breast Group: Breast International Group (BIG); Non-Financial Interests, Member: EORTC Breast Group; Other, Unrestricted funding for organization of academic symposium: Agendia, AstraZeneca-MSD, Daiichi, Eisai, Exact Sciences, Lilly, Pierre Fabre, Gilead, Novartis, Pfizer, Roche, Seagen, Viatris, Vifor; Other, Support for participation in international congress: AstraZeneca, Daiichi, Gilead, Pierre Fabre, Roche, Lilly. N.T. Ueno: Financial Interests, Personal, Research Funding: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer Ingelheim, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, 1TRIALSP, S.L.; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.,; Financial Interests, Institutional, Local PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Novartis; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. K. Papazisis: Financial Interests, Personal, Invited Speaker: MSD, Gilead, AstraZeneca, Novartis, Novartis, Genesis, Eli Lilly, Roche; Financial Interests, Personal, Advisory Board: MSD, Eli Lilly, GSK; Financial Interests, Personal, Research Grant: MSD, AstraZeneca, Novartis, Eli Lilly, Daiichi Sankyo, Roche, GSK, NEKTAR, BMS, Boehringer Ingelheim, Sanofi, Eisai; Financial Interests, Personal, Advisory Role: Novartis, Ipsen. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: PUMA, NAPO, Mylan, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc., GSK, Sermonix Pharmaceuticals Ins., Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. N. Harbeck: Financial Interests, Personal and Institutional, Other, Honoraria for lectures and/or consulting; Clinical Trials: Amgen, AstraZeneca, Daiichi Sankyo, EPG Communication, Gilead, Eli Lilly, Medscape, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Seagen, Sanofi, Springer, Zuelligpharma, Viatris. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. C.M.A. Orbegoso, L. Yung, F. Cheng, Y. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. D.A. Cameron: Financial Interests, Institutional, Advisory Board: Roche, Pfizer, AstraZeneca, Daiichi Sankyo, SeaGen, Synthon, Zymeworks; Financial Interests, Institutional, Other, Have done advisory boards, spoken at a webinar and invovled in a manuscript with Lilly - all recompense to my institution: Lilly; Financial Interests, Institutional, Other, Have done advisory boards and been involved in a health economic analysis and publication. All recompense to my institution: Novartis; Financial Interests, Institutional, Coordinating PI, funding and drug for UK participation in a french led Novartis funded study.Insitutional funding recieved for consultancy work: Novartis; Non-Financial Interests, Principal Investigator, one of three PIs for the Ameera-6 trial - which has now closed early as the company have stopped all development of the drug: Sanofi; Other, Chair of the board of this small Scottish charity for secondary breast cancer: Make Seconds Count; Other, Chair of the Board of B.I.G. - a group of international breast cancer research groups: Breast International Group; Other,Chair of the European Breast Cancer Council which organises the bi-annual EBCC meetings: EBCC. All other authors have declared no conflicts of interest.