Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study
Abstract
PURPOSE The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non–small cell lung cancer (NSCLC). METHODS Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m 2 once every 3 weeks. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Objective response rate, duration of response, and safety were secondary end points. RESULTS In total, 299 and 305 patients were randomly assigned to receive Dato-DXd or docetaxel, respectively. The median PFS was 4.4 months (95% CI, 4.2 to 5.6) with Dato-DXd and 3.7 months (95% CI, 2.9 to 4.2) with docetaxel (hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.91]; P = .004). The median OS was 12.9 months (95% CI, 11.0 to 13.9) and 11.8 months (95% CI, 10.1 to 12.8), respectively (HR, 0.94 [95% CI, 0.78 to 1.14]; P = .530). In the prespecified nonsquamous histology subgroup, the median PFS was 5.5 versus 3.6 months (HR, 0.63 [95% CI, 0.51 to 0.79]) and the median OS was 14.6 versus 12.3 months (HR, 0.84 [95% CI, 0.68 to 1.05]). In the squamous histology subgroup, the median PFS was 2.8 versus 3.9 months (HR, 1.41 [95% CI, 0.95 to 2.08]) and the median OS was 7.6 versus 9.4 months (HR, 1.32 [95% CI, 0.91 to 1.92]). Grade ≥3 treatment-related adverse events occurred in 25.6% and 42.1% of patients, and any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8.8% and 4.1% of patients, in the Dato-DXd and docetaxel groups, respectively. CONCLUSION Dato-DXd significantly improved PFS versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology. OS showed a numerical benefit but did not reach statistical significance. No unexpected safety signals were observed.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (138)
Kentaro Tanaka
Óscar Juan-Vidal
Michael Chargualaf
Daiichi Sankyo, Basking Ridge, NJ
Yong Zhang
Paul Howarth
Daiichi Sankyo, Inc, Basking Ridge, NJ
Deise Uema
AbbVie, Inc., North Chicago, IL
Gaston Lucas Martinengo
Juan Puig
Daniel Brungs
Medical Oncology, Cancer Care Wollongong and Graduate School of Medicine, University of Wollongong, Wollongong, Australia
Bo Gao
College of Energy, Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory of Advanced Negative Carbon Technologies, Soochow University, Suzhou, China.
Adnan Nagria
Chris Karapetis
Sagun Parakh
Department of Medical Oncology, Austin Hospital, Heidelberg, ACT, Australia
John Park
Nebraska Methodist Hospital, Omaha
Gaetan Catala
Frederic Forget
Centre Hospitalier de l'Ardenne, Libramont-Chevigny, Belgium
Sebahat Ocak
Naveen Basappa
Geoffrey Liu
Ines Menjak
Benjamin Shieh
Shun Lu
Feng Luo
National Key Laboratory of Uranium Resources Exploration-Mining and Nuclear Remote Sensing
Hongmei Sun
Institute of Special Economic Animals and Plants, Chinese Academy of Agricultural Sciences
Jialei Wang
Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai
Yu Yao
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering
Milada Zemanova
Jaafar Bennouna
Hôpital Foch, Suresnes, France
Nicolas Girard
Institut Curie, Institut du Thorax Curie-Montsouris, Paris
Laurent Greillier
Assistance Publique–Hôpitaux de Marseille, Hôpital Nord, Marseille, France
Corinne Lamour
Hervé Lena
Pneumology Department, Centre Hospitalier Universitaire Rennes, Université Rennes 1, INSERM, UMR_S 1242, Centre Eugene Marquis, Rennes, France
Celine Mascaux
Pulmonology Department, Strasbourg University Hospitals; Regenerative Nanomedicine, INSERM U1260, Strasbourg University, Strasbourg, NA, France
Julien Mazières
Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France
Denis Moro-Sibilot
CHU Grenoble Alpes, Hôpital Albert Michallon, La Tronche, France
Maurice Pérol
Elvire Pons-Tostivint
Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France
Virginie Westeel
Pneumology department, CHU Besançon - Hôpital J. MINJOZ, Besançon, France
Akin Atmaca
Christine Greil
1University of Freiburg, Hematology, Oncology and Stem Cell Transplantation, Department of Medicine I, Faculty of Medicine, Freiburg, Germany
Niels Reinmuth
Thoracic Oncology, Asklepios Clinics Munich-Gauting, Gauting, Germany
Christian Schumann
Thomas Wehler
Universitätsklinikum Gießen und Marburg GmbH Standort Gießen, Gießen, Germany
Juergen Wolf
Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany
James Ho
Department of Chemical and Biological Engineering
Csaba Bocskei
Federico Cappuzzo
Filippo de Marinis
Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan
Claudia Proto
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
Manlio Mencoboni
Silvia Novello
Stefania Salvagni
IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
Hector Soto Parra
Azienda Ospedaliero—Universitaria “Policlinico—Vittorio Emanuele”, Catania, Italy
Haruko Daga
Yasushi Goto
Hidetoshi Hayashi
Satoru Kitazono
Kiyotaka Yoh
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
Ryo Ko
Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
Masashi Kondo
Toshiyuki Kozuki
Takayasu Kurata
Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan
Hideaki Mizutani
Saitama Cancer Center, Saitama, Japan
Kadoaki Ohashi
Satoshi Oizumi
Satoshi Sakaguchi
Hiroaki Ozasa
Shunichi Sugawara
Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan
Yuichi Tambo
Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa-Shi, Japan
Motohiro Tamiya
Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
Hiroshi Tanaka
Isamu Okamoto
Froylan López-López
Francisco Javier Ramírez Godinez
Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico
Jeronimo Rafael Rodriguez Cid
Oncology Center, Medica Sur Hospital, Mexico City, Mexico
Robin Cornelissen
Erasmus MC Cancer Institute, Rotterdam, Netherlands
Steven Gans
Jos Stigt
Department of Respiratory Medicine, Isala Hospital, Zwolle, Netherlands
Dariusz Kowalski
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Klinika Nowotworow Pluca i Klatki Piersiowej, Warsaw, Poland
Anna Lowczak
Janusz Milanowski
Robert Mróz
Rodryg Ramlau
Mirelis Acosta-Rivera
Myung-Ju Ahn
Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Yee Soo Chae
Department of Oncology and Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, South Korea
Min Hee Hong
Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Jin-Hyoung Kang
Sang-We Kim
Asan Medical Center, Seoul, South Korea
Jin-Soo Kim
Se Hyun Kim
Ki Hyeong Lee
Chungbuk National University Hospital, Cheongju-si, North Chungcheong, Cheongju, South Korea
Yun Gyoo Lee
Byoung Yong Shim
Evgeniy Ledin
Elena Poddubskaya
VitaMed LLC, Moscow, Russia
Boon Yeow Daniel Chan
Amit Jain
1NMMC, Internal medicine, Tupelo, United States
Chee Seng Tan
María Carmen Areses
Manuel Cobo
Medical Oncology Section, Hospital Regional Universitario Carlos Haya, Málaga, Spain
Manuel Domine
Department of Oncology, Fundación Jiménez Díaz, Campus Hospitalario, IIS-FJD, Universidad Autónoma de Madrid, Madrid, Spain
Enriqueta Felip
Medical Oncology Service, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona
José Fuentes Pradera
Dolores Isla
Hospital Clínico Lozano Blesa, Zaragoza, Spain
Oscar Juan Vidal
Margarita Majem
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Luis Paz-Ares
Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid
Mariano Provencio
Hospital Universitario Puerta de Hierro, Madrid
Noemi Reguart
Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain
David Vicente Baz
Ferdinando Cerciello
Martin Früh
Wen-Cheng Chang
Gee-Chen Chang
School of Medicine and Institute of Medicine, Chung Shan Medical University and Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
Wen-Tsung Huang
Chi Mei Chest Hospital, Tainan, Taiwan
Chien-Chung Ling
Yu-Feng Wei
E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
Tsung-Ying Yang
Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
Tanya Ahmad
Fabio Gomes
Talal Mansy
Debora Bruno
Michael Castine
Bruno Fang
Marina Garassino
Department of Medicine, Hematology-Oncology Section, Thoracic Oncology Program, The University of Chicago Medicine & Biological Sciences, Chicago, IL
Richard Hall
1University of Virginia, Charlottesville, United States
Balazs Halmos
Khawaja Jahangir
Melissa Johnson
Sarah Cannon Research Institute, Nashville
Tirrell Johnson
Sujith Kalmadi
William Lawler
Aaron Lisberg
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA
Ahad Sadiq
Jacob Sands
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Benjamin Solomon
Andrea Veatch