Yi-Long Wu1, Thomas John2, Christian Grohe3, Margarita Majem4, Jonathan W Goldman5, Sang-We Kim6, Terufumi Kato7, Konstantin Laktionov8, Huu Vinh Vu9, Zhijie Wang10, Shun Lu11, Kye Young Lee12, Charuwan Akewanlop13, Chong-Jen Yu14, Filippo de Marinis15, Laura Bonanno16, Manuel Domine17, Frances A Shepherd18, Lingmin Zeng19, Ajlan Atasoy20, Roy S Herbst21, Masahiro Tsuboi22. 1. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. Electronic address: syylwu@live.cn. 2. Department of Medical Oncology, Austin Health, Melbourne, Australia. 3. Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin, Germany. 4. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 5. David Geffen School of Medicine at University of California, Los Angeles, California. 6. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 7. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 8. Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russia. 9. Department of Thoracic Surgery, Choray Hospital, Ho Chi Minh City, Vietnam. 10. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China. 11. Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China. 12. Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, South Korea. 13. Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand. 14. Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch and National Taiwan University College of Medicine, Taipei, Taiwan. 15. Thoracic Oncology Division, European Institute of Oncology (IEO), IRCCS, Milan, Italy. 16. Medical Oncology 2, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy. 17. Oncology Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain. 18. Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada. 19. Late Oncology Statistics, AstraZeneca, Gaithersburg, Maryland. 20. Late Oncology Research & Development, AstraZeneca, Cambridge, United Kingdom. 21. Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, Connecticut. 22. Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
INTRODUCTION: Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA. METHODS: Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB-IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage. RESULTS: Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10-0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13-0.40), regardless of disease stage. CONCLUSIONS: These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.
INTRODUCTION: Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA. METHODS: Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB-IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage. RESULTS: Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10-0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13-0.40), regardless of disease stage. CONCLUSIONS: These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.
Authors: Marco de Scordilli; Anna Michelotti; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-29 Impact factor: 6.208
Authors: Kenneth L Kehl; David Zahrieh; Ping Yang; Shauna L Hillman; Angelina D Tan; Jacob M Sands; Geoffrey R Oxnard; Erin A Gillaspie; Dennis Wigle; Shakun Malik; Thomas E Stinchcombe; Suresh S Ramalingam; Karen Kelly; Ramaswamy Govindan; Sumithra J Mandrekar; Raymond U Osarogiagbon; David Kozono Journal: JAMA Oncol Date: 2022-05-01 Impact factor: 33.006