Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor–Positive Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: Primary Results From TROPION-Breast01
Abstract
PURPOSE The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. METHODS Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). RESULTS Patients were randomly assigned to Dato-DXd (n = 365) or ICC (n = 367). Dato-DXd significantly reduced the risk of progression or death versus ICC (PFS by BICR hazard ratio [HR], 0.63 [95% CI, 0.52 to 0.76]; P < .0001). Consistent PFS benefit was observed across subgroups. Although OS data were not mature, a trend favoring Dato-DXd was observed (HR, 0.84 [95% CI, 0.62 to 1.14]). The rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was lower than ICC (20.8% v 44.7%). The most common TRAEs (any grade; grade ≥3) were nausea (51.1%; 1.4%) and stomatitis (50%; 6.4%) with Dato-DXd and neutropenia (grouped term, 42.5%; 30.8%) with ICC. CONCLUSION Patients receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS and a favorable and manageable safety profile, compared with ICC. Results support Dato-DXd as a novel treatment option for patients with inoperable/metastatic HR+/HER2‒ breast cancer who have received one to two previous lines of chemotherapy in this setting.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (181)
Lu Xu
Rick M. Fairhurst
AstraZeneca, Gaithersburg, MD
Sabrina Khan
AstraZeneca, Gaithersburg, MD
Neelima Denduluri
AstraZeneca, Gaithersburg, MD
Betiana Romitelli
Ernesto Korbenfeld
British Hospital of Buenos Aires, Central British Hospital, Buenos Aires
Cristian Buono
Arturo Barbero
Geronimo Rosselli
Sergio Daniele
Sandra Anabel Ostoich
Hans Wildiers
Kevin Punie
Medical Oncology, Oncology Center Antwerp, Ziekenhuis aan de Stroom, Antwerp, Belgium
Joelle Collignon
Guy Jerusalem
Andrea Gombos
Institut Jules Bordet and Université Libre de Bruxelles, Brussels, Belgium
Giuliano Borges
Catarina Pesquisa Clínica–Clínica de Neoplasias, Santa Catarina, Brazil
Pedro Emanuel Rubini Liedke
Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
Marcelle Cesca
Patricia Beato
Laura Testa
Instituto D’Or de Pesquisa e Ensino (IDOR), São Paulo, Brazil
Helio Pinczowski
Liane Rapatoni
University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Debora Jardim
José Bines
David W. Cescon
Princess Margaret Cancer Centre, University Health Network, Toronto
Jamil Asselah
Gerald Bronfman Department of Oncology, McGill University Health Centre, Cedars Cancer Center, Montreal, QC, Canada
Andre Blais
Joanne Yu
Jennifer Friedmann
Jewish General Hospital, McGill University, Montreal, QC, Canada
Cristiano Ferrario
Jewish General Hospital, McGill University, Montreal, QC, Canada
Binghe Xu
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
Shusen Wang
Qingyuan Zhang
Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China
Zefei Jiang
Department of Breast Cancer, Fifth Medical Center of People’s Liberation Army General Hospital, Beijing
Zhongsheng Tong
Quchang Ouyang
Jingfen Wang
Tingjing Yao
Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
Yongsheng Wang
Division of Thoracic Tumor Multimodality Treatment Cancer Center, West China Hospital, Sichuan University
Xiaojia Wang
Department of Mechanical Engineering
Meili Sun
Central Hospital Affiliated to Shandong First Medical University, Jinan, China
Hui Li
Shu Wang
Yuan Sheng
Aimin Zang
Department of Oncology, Affiliated Hospital of Hebei University, Baoding, China
Zhanmin Zhang
Wenyan Chen
Xian Wang
School of Chemistry and Materials Science
Zhong Ouyang
Wei Li
Barbara Pistilli
Department of Cancer Medicine, Gustave Roussy, Villejuif, France
Thomas Bachelot
Mony Ung
Université de Toulouse, Oncopole Claudius Regaud, IUCT-Oncopole, Department of Medical Oncology, Toulouse, France
Cristian Villanueva
Centre de Cancérologie du Grand Montpellier, Clinique Clementville, Montpellier, France
Delphine Garbay
Anne-Claire Hardy-Bessard
Audrey Mailliez
Department of Medical Oncology, Breast Cancer Unit, Centre Oscar Lambret, Lille, France
Stephanie Becourt
Centre Oscar Lambret, Lille, France
William Mina
Thomas Decker
16Oncological Practice, Ravensburg, Germany
Julia Radosa
Andreas Schneeweiss
National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
Michael Braun
Bahriye Aktas
Gábor Rubovszky
Zsuzsanna Pápai
Tibor Csoszi
Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
Yousuf Al-Farhat
Department of Oncology, Tolna Vármegyei Balassa János Kórház, Szekszárd, Tolna, Hungary
Ankit Patel
Department of Computer Science, Rice University
Vineet Gupta
Richu Sharma
Ujala Cygnus JK Medicity, Jammu, India
Chandrakanth Mosale Venkatesha
Shailesh Bondarde
Apex Wellness Hospital, Nashik, India
Somnath Roy
Tata Medical Center, Kolkata, India
Nikhil Ghadyalpatil
Apollo Hospitals, Hyderabad, India
Lalit Sharma
Rajani Yedla
Michelino De Laurentiis
Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale,” Naples, Italy
Ida Paris
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Claudio Zamagni
IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
Valentina Guarneri
Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy
Icro Meattini
Azienda Ospedaliero Universitaria Careggi, University of Florence, Firenze, Italy
Marco Colleoni
Giampaolo Bianchini
IRCCS Ospedale San Raffaele, Milan
Ugo De Giorgi
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy
Filippo Montemurro
F. Hoffmann-La Roche Ltd, Basel, Switzerland
Elena Geuna
Laura Biganzoli
Junji Tsurutani
The Innovative Center of Translational Research and Clinical Science for Cancer Therapy, Showa Medical University Hospital, Tokyo, Japan
Masaya Hattori
Aichi Cancer Center, Nagoya, Japan
Yukinori Ozaki
Akihiko Shimomura
Risako Komata, MD; Kenju Ando, MD, PhD; Akihiko Shimomura, MD, PhD; and Chikako Shimizu, MD, PhD, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan
Naoki Niikura
Department of Breast Oncology, Tokai University School of Medicine, Kanagawa, Japan
Mitsuya Itoh
Tetsuhiko Taira
Department of Medical Oncology, Hakuaikai Social Medical Corporation, Sagara Hospital, Kagoshima, Japan
Toru Mukohara
Kenjiro Aogi
Tsutomu Iwasa
Kindai University Hospital, Osaka, Japan
Eriko Tokunaga
National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
Shigehira Saji
Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan
Nobuko Kawaguchi
Toshinari Yamashita
Department of Breast Surgery and Oncology, Kanagawa Cancer Center, Yokohama, Japan
Kenichi Inoue
Takahiro Nakayama
Osaka International Cancer Institute, Osaka, Japan
Kenichi Watanabe
Masayuki Nagahashi
Kan Yonemori
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
Jan Drooger
Inge Konings
Agnès van de Wouw
Zbigniew Nowecki
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Warsaw, Poland
Ewa Chmielowska
Iwona Danielewicz
Department of Clinical Oncology, Maritime Hospital in Gdynia, Gdynia, Poland
Jacek Jassem
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
Ewa Kalinka
Bogumiła Czartoryska-Arłukowicz
Bogusława Karaszewska
Mariusz Kwiatkowski
Seock-Ah Im
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea
Joo Hyuk Sohn
Yeon Hee Park
Keun Seok Lee
National Cancer Center, Goyang, South Korea
Kyung Hae Jung
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Kyong Hwa Park
Jee Hung Kim
Daniil Stroyakovskiy
Moscow City Oncology Hospital No. 62, Moscow
Elena Artamonova
National Medical Research Center of Oncology Named After N.N. Blokhin, Moscow, Russian Federation
Martha Mekebeb-Reuter
Bernardo Rapoport
Medical Oncology Centre of Rosebank, Clinical and Translational Research Unit, Saxonwold, South Africa
Elizabeth Schoeman
Maria Coccia-Portugal
Rofhiwa Mathiba
Medical Oncology Department, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
Sonia Pernas
Institut Català d’Oncologia–Institut d’Investigació Biomèdica de Bellvitge, L’Hospitalet, Barcelona
Noelia Martinez Janez
Barbara Adamo
Institute of Cancer and Blood Diseases, Hospital Clinic of Barcelona / Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute IDIBAPS, Barcelona, Spain
Begoña Bermejo de las Heras
José Ángel García Sáenz
Manuel Ruíz Borrego
Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain
María Emilia Domínguez
Begoña Jiménez Rodríguez
Silvia Antolín Novoa
Complejo Hospitalario Universitario a Coruña (CHUAC); GEICAM Spanish Breast Cancer Group, A Coruna, Spain
Elena Galve Calvo
Medical Oncology Service, Hospital Universitario Basurto (OSI Bilbao-Basurto), Bilbao, Spain
Javier Cortes Castan
Juan Lucas Bayo Calero
Hospital Juan Ramón Jiménez, Huelva, Spain
Shin-Cheh Chen
Chang Gung Medical Foundation Linkou Branch, Taoyuan City, Taiwan
Ling-Ming Tseng
Yen-Shen Lu
Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch
Wei-Pang Chung
National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Yuan-Ching Chang
Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
Chien-Ting Liu
Hwei-Chung Wang
Kun-Ming Rau
Charles Comins
Jeremy Braybrooke
Annabel Borley
Ciara O'Brien
The Christie NHS Foundation Trust, Manchester, United Kingdom
Caroline Michie
Edinburgh Cancer Center Edinburgh UK
Peter Schmid
Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London
Sophie McGrath
Duncan Wheatley
Royal Cornwall Hospital NHS Trust, Cornwall, United Kingdom
Mukesh Mukesh
Sachin Trivedi
Syed Karim
KCH Dubai, Dubai, United Arab Emirates
Pavel Bezecny
Aditya Bardia
Hope S. Rugo
City of Hope Comprehensive Cancer Center, Duarte, CA
Kevin Kalinsky
Winship Cancer Institute, Emory University, Atlanta
Erika Hamilton
Komal Jhaveri
Memorial Sloan Kettering Cancer Center, New York
Yuan Yuan
Niki Patel
Joanne Mortimer
Sara Tolaney
Amy Vander Woude
Gail Wright
Fauzia Riaz
Stanford Cancer Institute, Stanford, CA
Apurva Pandey
Halle Moore
1Cleveland Clinic, Cleveland, United States
Masey Ross
Kelly McCann