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Programme

12 February 2025

Welcome and introduction, Scientific background and context

Chair – Peter Schmid

Clinical trial data presentation, Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial

Barbara Pistilli

Critical analysis and perspectives

Veronique Dieras

AACR expert commentary

Sarat Chandarlapaty

Discussion and Q&A

All speakers

Abstract

VP1-2025: Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial

B. Pistilli1, K. Jhaveri2, S-A. Im3, S. Pernas Simon4, M. De Laurentiis5, S. Wang6, N. Martinez7, G. Santos Borges8, D. Cescon9, M. Hattori10, Y-S. Lu11, E. Hamilton12, Q. Zhang13, J. Tsurutani14, K. Kalinsky15, L. Xu16, S. Khan17, H.S. Rugo18, B. Xu19, A. Bardia20

1 Medical Oncology Department, Gustave Roussy Cancer Center, Villejuif, France
2 Medicine Department, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
3 Internal Medicine Department, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
4 Medical Oncology Breast Unit, Institut Català d'Oncologia, IDIBELL, Barcelona, Spain
5 Department of Breast and Thoracic Oncology, Istituto Nazionale Tumori Napoli IRCCS "Fondazione Pascale", Naples, Italy
6 Medical Oncology, Cancer Center of Sun Yat-sen University, Guangzhou, China
7 Ramón y Cajal University Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
8 Medical Oncology, Catarina Pesquisa Clínica, Santa C, SC, Brazil
9 Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre/UHN, Toronto, Canada
10 Department of Breast Oncology, Aichi Cancer Center, Nagoya, Aichi, Japan
11 Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan
12 Department of Drug Development, Sarah Cannon Research Institute, Nashville, TN, United States of America
13 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
14 Advanced Cancer Translation Research Institute, Showa University, Shinagawa-ku, Japan
15 Hematology & Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, United States of America
16 Biostatistics, AstraZeneca, New York, NY, United States of America
17 Late Phase Oncology R&D, AstraZeneca, Gaithersburg, MD, United States of America
18 Department of Medicine, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, United States of America
19 Department of Medical Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
20 Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, United States of America

Published: February 12, 2025
DOI: https//doi.org/10.1016/j.annonc.2025.01.009 Download PDF

Background

TROPION-Breast01 (NCT05104866) demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) by blinded independent central review (BICR) with the TROP2-directed ADC Dato-DXd vs investigator’s choice of CT (ICC) in patients (pts) with previously treated, inoperable/metastatic HR+/HER2– BC (HR 0.63 [95% CI 0.52–0.76]; p<0.0001). We report the final OS analysis and updated safety.

Methods

Pts with inoperable/metastatic HR+/HER2‒ BC, who had disease progression on endocrine therapy (ET) and for whom ET was unsuitable, and had received 1‒2 prior lines of CT, were randomised 1:1 to Dato-DXd (6 mg/kg Q3W) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary endpoints were PFS by BICR and OS. Secondary endpoints included PFS by investigator and PFS2.

Results

At data cutoff (24 Jul 2024), median follow-up was 22.8 months. Results are shown in the Table. OS for the Dato-DXd vs ICC arm did not reach statistical significance (HR 1.01 [95% CI 0.83–1.22]; p=0.94). Use of ADCs (trastuzumab deruxtecan & sacituzumab govitecan) as subsequent therapy was imbalanced: 12.3% in Dato-DXd arm vs 24.0% in ICC arm. OS sensitivity analysis for subsequent ADC use showed an adjusted HR of 0.86 (95% CI 0.70‒1.06). Lower rates of grade ≥3 TRAEs (22.2% vs 45.6%) and TRAEs leading to dose reduction (24.2% vs 30.2%) occurred with Dato-DXd vs ICC. TRAEs leading to discontinuation were similar (3.3% vs 2.6%).
Conclusions: TROPION-Breast01 PFS was statistically significant, although OS was not statistically significant. The totality of efficacy and safety data support Dato-DXd as a potential new treatment option for pts with previously treated, inoperable/metastatic HR+/HER2‒ BC.

Conclusions

TROPION-Breast01 PFS was statistically significant, although OS was not statistically significant. The totality of efficacy and safety data support Dato-DXd as a potential new treatment option for pts with previously treated, inoperable/metastatic HR+/HER2‒ BC.

	Dato-DXd	ICC
	N=365	N=367
OS
Median OS (95% CI), mo	18.6 (17.3–20.1)	18.3 (17.3–20.5)
HR (95% CI)*	1.01 (0.83–1.22)
Prespecified OS sensitivity analysis
HR (stratification per eCRF) (95% CI)	0.99 (0.82–1.20)
Subsequent therapy, %
Any	73.7	78.7
ADC	12.3	24.0
Trastuzumab deruxtecan	9.3	21.8
Sacituzumab govitecan	4.1	7.1
Post-hoc OS sensitivity analysis adjusted for subsequent ADC therapy†
Median OS, mo	19.1	17.5
HR (95% CI)	0.86 (0.70‒1.06)
PFS by investigator
HR (95% CI)	0.64 (0.55–0.76)
PFS2
HR (95% CI)	0.76 (0.63–0.93)
Data cutoff: 24 Jul 2024. *Stratification per interactive response technology (IRT). †Using Inverse Probability Censoring Weighting (IPCW). eCRF, electronic case report form.

Clinical trial identification

NCT05104866; release date November 3, 2021.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP).

Legal entity responsible for the study

AstraZeneca PLC.
Funding

This trial is sponsored by AstraZeneca. In July 2020, Daiichi Sankyo entered into a global development and commercialization collaboration with AstraZeneca for datopotamab deruxtecan (Dato-DXd).

Disclosure

B. Pistilli: Financial Interests, Institutional, Advisory Role, Consulting fees: AstraZeneca, Seagen, Gilead, Novartis, Lilly, MSD, Daiichi Sankyo, Olema; Financial Interests, Personal, Advisory Role, Consulting fees: Pierre Fabre; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Daiichi Sankyo, Gilead, Seagen, MSD; Financial Interests, Personal, Other, Travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo, Pfizer. K. Jhaveri: Financial Interests, Personal, Advisory Role, Consulting: Novartis, Pfizer, AstraZeneca, Jounce Therapeutics, Synthon, Intellisphere, Bristol Myers Squibb, Genentech, AbbVie, Lilly, Blueprint Medicines, Seagen, Daiichi Sankyo, Biotheranostics, Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead Sciences, Scorpion Therapeutics, Eisai; Financial Interests, Institutional, Funding, Research funding: Novartis, Genentech, Debiopharm Group, ADC Therapeutics, Pfizer, Novita Pharmaceuticals, Clovis Oncology, Lilly, Zymeworks, Immunomedics, Puma Biotechnology, VelosBio/Merck, AstraZeneca, Context Therapeutics, Scorpion Therapeutics, Blueprint Medicines; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Taiho Pharmaceutical, Jounce Therapeutics, Pfizer, AstraZeneca, Intellisphere, Lilly, Gilead Sciences, Genentech/Roche. S. Im: Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca, Novartis, Roche/Genentech, Eisai, Pfizer, Amgen, Hanmi, Lilly, MSD, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical, Eisai, Boryung Pharmaceuticals; Financial Interests, Personal, Other: Roche. S. Pernas Simon: Financial Interests, Personal, Advisory Role, Consulting: Seagen, Pfizer, Pierre Fabre, Daiichi Sankyo/AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly, Roche, Gilead Sciences, Pfizer, Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Funding, Research funding: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences, AstraZeneca, Roche, Pfizer; Non-Financial Interests, Personal, Other, Uncompensated Relationships: SOLTI. M. De Laurentiis: Financial Interests, Personal, Stocks/Shares: Arvinas; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer, Lilly, Pierre Fabre, AstraZeneca, MSD, Seagen, Gilead Sciences, Ipsen, Exact Sciences, TOMA Biosciences, Daiichi Sankyo Europe GmbH, Veracyte; Financial Interests, Personal, Advisory Role, Consulting: Roche, Novartis, Pfizer, Lilly, AstraZeneca, MSD, Pierre Fabre, Seagen, Gilead Sciences, Ipsen, Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Funding, Research funding: Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Bristol Myers Squibb, Genzyme, AstraZeneca; Financial Interests, Personal, Funding, Research funding: Lilly. S. Wang: Financial Interests, Personal, Advisory Role, Consulting: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, AstraZeneca, Novartis, Lilly; Financial Interests, Personal, Funding, Research funding: Pfizer, AstraZeneca. N. Martinez: Financial Interests, Personal, Advisory Role, Consulting: Pfizer; Financial Interests, Personal, Funding, Research funding: Pfizer, Novartis, Lilly. D. Cescon: Financial Interests, Personal, Advisory Role, Consulting: Pfizer, AstraZeneca, Novartis, GlaxoSmithKline, Merck, Gilead Sciences, GenomeRx, NeoGenomics, Lilly, SAGA Diagnostics, Daiichi Sankyo Europe GmbH; Financial Interests, Institutional, Funding, Research funding: Merck, Roche/Genentech, GSK, Pfizer, NeoGenomics, AstraZeneca, Gilead Sciences, Knight Therapeutics, Guardant Health, ProteinQure, GRAIL. M. Hattori: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD K.K. Y. Lu: Financial Interests, Personal, Other, Honoraria: Pfizer, Roche, Merck Sharp & Dohme, Novartis, Lilly, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, EuroPharma; Financial Interests, Personal, Advisory Role, Consulting: Pfizer, Roche, Novartis, Lilly; Financial Interests, Institutional, Funding, Research funding: Novartis, Merck Sharp & Dohme, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis. E. Hamilton: Financial Interests, Institutional, Advisory Role, Consulting: Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis GmbH, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Zentalis, Jefferies, Tempus, Arvinas, Circle Pharma, Janssen, Johnson and Johnson; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millennium, TapImmune Inc, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, AbbVie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceutical, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Sutro Biopharma, Zenith Epigenetics, Arvinas, Harpoon, Black Diamond Therapeutics, Orinove, Molecular Templates, Seagen, Compugen, G1 Therapeutics, Karyopharm Therapeutics, Dana Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akeso Biopharma, ADC Therapeutics , AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repertoire Immune Medicines, Treadwell Therapeutics, Jacobio, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, ProfoundBio, Cullinan Oncology, Bristol Myers Squibb; Financial Interests, Personal, Funding, Research funding: Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics. J. Tsurutani: Financial Interests, Personal, Other, Honoraria: Kyowa Kirin, Eisai, Chugai Pharma, Taiho Pharmaceutical, Nihon Kayaku, Lilly Japan, Daiichi Sankyo, Pfizer; Consulting or Advisory Role: Daiichi Sankyo, Lilly, AstraZeneca/Daiichi Sankyo, Seagen; Financial Interests, Personal, Funding, Research funding: Eisai, Boehringer Ingelheim, Lilly, MSD Oncology, Kyowa Kirin, Daiichi Sankyo, Chugai Pharma, Nihon Kayaku, West Japan Oncology Group, Sant Joan de Déu Research Foundation (FSJD). K. Kalinsky: Financial Interests, Personal, Full or part-time Employment: EQRx; Financial Interests, Personal, Stocks/Shares: EQRx; Financial Interests, Personal, Advisory Role, Consulting: Lilly, Novartis, AstraZeneca, Genentech/Roche, Merck, Daiichi Sankyo/AstraZeneca, Menarini Silicon Biosystems, Myovant Sciences, Takeda, Prelude Therapeutics, RayzeBio, eFFECTOR Therapeutics, Cullinan Oncology, Gilead Sciences, Relay Therapeutics, Regor, Puma Biotechnology, Mersana, Pfizer, Biotheranostics; Financial Interests, Personal, Funding, Research funding: Novartis, Genentech/Roche, Lilly, Seagen, AstraZeneca, Daiichi Sankyo, Ascentage Pharma. L. Xu, S. Khan: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H.S. Rugo: Financial Interests, Personal, Other, Honoraria: Mylan/Viatris, Chugai Pharma; Financial Interests, Personal, Advisory Role, Consulting: Napo Pharmaceuticals, Puma Biotechnology, Sanofi; Financial Interests, Institutional, Funding, Research funding: OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffmann-La Roche AG/Genentech, Inc., Stemline Therapeutics, Ambryx. B. Xu: Financial Interests, Personal, Advisory Role, Consulting: Novartis, AstraZeneca. A. Bardia: Financial Interests, Personal, Advisory Role, Consulting: Genentech, Merck, Mersana, Sanofi, Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Advisory Role, Consulting: Novartis, Genentech/Roche, Pfizer, Radius Health, Innocrin Pharma, Lilly, Gilead Sciences, Menarini; Financial Interests, Institutional, Funding, Research funding: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, AstraZeneca/Daiichi Sankyo. All other authors have declared no conflicts of interest.