Neoadjuvant Osimertinib for Resectable <i>EGFR</i> -Mutated Non–Small Cell Lung Cancer
Abstract
PURPOSE Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor ( EGFR )–mutated non–small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes. METHODS In this randomized, controlled, phase III study, patients with resectable, EGFR -mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point. RESULTS Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; P < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified. CONCLUSION Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR -mutated, stage II-IIIB NSCLC.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (123)
Collin M. Blakely
Yuri Rukazenkov
Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom
Xiangning Huang
Biometrics, Late-stage Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
Anupriya Dayal
Late-stage Development, Oncology R&D, AstraZeneca, Gaithersburg, MD
Gudrun Absenger
Maximilian J. Hochmair
Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria
Clarissa Baldotto
Instituto D´Or de Pesquisa e Ensino, Rio De Janeiro, Brazil
Georgia Fiuza Alencar Araripe
Jose Miziara
José Fernando Moura
Carlos H.A. Teixeira
Clinical Oncology Department, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
Nataliya Chilingirova
Rossitza Krasteva
Velko Minchev
UMHAT “Sofiamed”, Sofia, Bulgaria
Marc de Perrot
Jonathan Spicer
Marcelo Garrido
Hemato-Oncology Department, SAGA Clinical Trial Center and Universidad Mayor, Santiago, Chile
María Paz Saavedra
Orlandi Oncología, Santiago, Chile
Kaican Cai
Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Chang Chen
Ke-Neng Chen
State Key Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing
Qixun Chen
Zhejiang Cancer Hospital
Chao Cheng
School of Life Sciences, Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, and Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University
Duan Hongbing
Wentao Fang
Shanghai East Hospital, Tongji University, Shanghai, China
Yongtao Han
Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
Jianxing He
State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease National Center for Respiratory Medicine Guangzhou Institute of Respiratory Health Guangzhou China
Gaofeng Li
Shanqing Li
Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing
Quan Lin
Lunxu Liu
Buhai Wang
Jingdi Wang
Qun Wang
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research
Wenxiang Wang
RemeGen, Yantai, China
Ming Wu
Nan Wu
Ligang Xing
Shandong Cancer Hospital, Jinan, China
Runxiang Yang
Department of Internal Medicine I, Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China
Bentong Yu
Department of Thoracic Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China
Wei Zhang
Jun Zhao
Department of Thoracic Oncology Beijing Cancer Hospital Beijing China
Ming Zhou
Centre for Catalysis and Clean Energy, Gold Coast Campus
Sigolène Galland-Girodet
Frank Griesinger
Department of Hematology and Oncology, Pius Hospital, University Medicine Oldenburg, Oldenburg, Germany
Justyna Rawluk
Wolfgang Schütte
Prabhat Malik
Bhavesh Poladia
Jair Bar
Institute of Oncology Chaim Sheba Medical Center Ramat Gan Israel
Elizabeth Dudnik
Diego Cortinovis
Domenico Galetta
IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
Silvia Novello
Sabrina Rossi
Norihiko Ikeda
Toshi Menju
Shuji Murakami
Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan
Morihito Okada
Jiro Okami
Akira Ono
Department of Microbiology & Immunology, University of Michigan Medical School
Miyako Satouchi
Shunichi Sugawara
Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan
Hidemi Suzuki
Kazuya Takamochi
Hiroshi Tanaka
Masahiro Tsuboi
National Cancer Center Hospital East, Kashiwa, Japan
Yasuhiro Tsutani
Kindai University, Osaka, Japan
Noriko Yanagitani
Department of Thoracic Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo
Yasushi Yatabe
Oscar Arrieta Rodriguez
Froylan López-López
Jerónimo Rodríguez Cid
Ana Fernandez
Jarosław Kołb-Sielecki
Jusang Kim
Sung Yong Lee
Seung Hyeun Lee
Sun-Hyo Park
Seung Soo Yoo
Seong Hoon Yoon
Department of Internal Medicine, Pusan National University, School of Medicine, and Yangsan Hospital, Yangsan, Republic of Korea
Tatiana Kleimenteva
Guzel Mukhametshina
SAHI Republican Clinical Cancer Dispensary, Ministry of Healthcare of the Republic of Tatarstan, Kazan, Russian Federation
Petr Yablonskiy
Manuel Domine Gomez
Alex Martinez-Marti
Department of Medical Oncology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Barcelona, Spain
Mariano Provencio Pulla
Ulrich Richter
Walter Weder
Gee Chen Chang
Chao-Hsun Chen
Yuh-Min Chen
Taipei Veterans General Hospital, Taipei, Taiwan
Han-Pin Kuo
Kang-Yun Lee
Jin-Yuan Shih
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
Touch Ativitavas
Manoch Buranachokphaisan
Jarin Chindaprasirt
Hataiwan Ratanabunjerdkul
Somcharoen Saeteng
Piyada Sitthideatphaiboon
Mustafa Dikilitas
Mehmet Sendur
Shobhit Baijal
Carles Escriu
Department of Medical Oncology, Clatterbridge Cancer Centre National Health Service Foundation Trust, Liverpool, United Kingdom
Arya Amini
City of Hope Medical Center, Duarte, CA
Ian Anderson
California Institute of Technology
Collin M. Blakley
Adam Bograd
Jamie E. Chaft
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Sanja Dacic
Department of Pathology, Yale School of Medicine, New Haven, CT
David Finley
Jonathan Goldman
University of California, Los Angeles, Los Angeles
Erminia Massarelli
City of Hope—Comprehensive Cancer Center, Duarte, CA
Julia Rotow
Catherine Shu
Alexander Spira
NEXT Oncology Virgina, Virgina Cancer Specialists Research Institute, Fairfax
Hien Nguyen
Nguyen Hoang Gia
Department of Medical Oncology, Hanoi Oncology Hospital, Hanoi, Vietnam
Nguyen Viet Nhung
Mai Tran
Diep Vo
Vinh Vu