PMID- 29151359 OWN - NLM STAT- MEDLINE DCOM- 20180118 LR - 20220603 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 378 IP - 2 DP - 2018 Jan 11 TI - Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. PG - 113-125 LID - 10.1056/NEJMoa1713137 [doi] AB - BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .). FAU - Soria, Jean-Charles AU - Soria JC AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Ohe, Yuichiro AU - Ohe Y AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Vansteenkiste, Johan AU - Vansteenkiste J AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Reungwetwattana, Thanyanan AU - Reungwetwattana T AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Chewaskulyong, Busyamas AU - Chewaskulyong B AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Lee, Ki Hyeong AU - Lee KH AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Dechaphunkul, Arunee AU - Dechaphunkul A AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Imamura, Fumio AU - Imamura F AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Nogami, Naoyuki AU - Nogami N AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Kurata, Takayasu AU - Kurata T AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Okamoto, Isamu AU - Okamoto I AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Zhou, Caicun AU - Zhou C AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Cho, Byoung Chul AU - Cho BC AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Cheng, Ying AU - Cheng Y AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Cho, Eun Kyung AU - Cho EK AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Voon, Pei Jye AU - Voon PJ AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Planchard, David AU - Planchard D AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Su, Wu-Chou AU - Su WC AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Gray, Jhanelle E AU - Gray JE AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Lee, Siow-Ming AU - Lee SM AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Hodge, Rachel AU - Hodge R AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Marotti, Marcelo AU - Marotti M AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Rukazenkov, Yuri AU - Rukazenkov Y AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). FAU - Ramalingam, Suresh S AU - Ramalingam SS AD - From Gustave Roussy Cancer Campus and University Paris-Sud, Orsay, France (J.-C.S., D.P.); the Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Y.O.), the Department of Thoracic Oncology, Osaka International Cancer Institute (F.I.), and the Department of Thoracic Oncology, Kansai Medical University Hospital (T.K.), Osaka, the Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama (N.N.), and the Research Institute for Diseases of the Chest, Graduate School of Medical Science, Kyushu University, Fukuoka (I.O.) - all in Japan; the Respiratory Oncology Unit, University Hospital KU Leuven, Leuven, Belgium (J.V.); Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok (T.R.), the Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai (B.C.), and the Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai (A.D.) - all in Thailand; the Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju (K.H.L.), the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (B.C.C.), and the Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon (E.K.C.) - all in South Korea; Pulmonary Hospital of Tongji University, Shanghai (C.Z.), and Jilin Provincial Cancer Hospital, Changchun (Y.C.) - both in China; Hospital Umum Sarawak, Kuching, Malaysia (P.J.V.); National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.E.G.); the Department of Oncology, University College London Hospitals Biomedical Research Centre, and the Cancer Research UK Lung Cancer Centre of Excellence, London (S.-M.L.), and AstraZeneca, Cambridge (R.H., M.M., Y.R.) - all in the United Kingdom; and Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.). CN - FLAURA Investigators LA - eng SI - ClinicalTrials.gov/NCT02296125 SI - ClinicalTrials.gov/NCT02296125 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171118 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 0 (Antineoplastic Agents) RN - 0 (Piperazines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - 3C06JJ0Z2O (osimertinib) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - S65743JHBS (Gefitinib) SB - IM CIN - N Engl J Med. 2018 Jan 11;378(2):192-193. doi: 10.1056/NEJMe1714580. PMID: 29320658 CIN - N Engl J Med. 2018 Mar 29;378(13):1261. doi: 10.1056/NEJMc1801669. PMID: 29595922 CIN - N Engl J Med. 2018 Mar 29;378(13):1261-2. doi: 10.1056/NEJMc1801669. PMID: 29595923 CIN - N Engl J Med. 2018 Mar 29;378(13):1262. doi: 10.1056/NEJMc1801669. PMID: 29595924 CIN - Ann Transl Med. 2018 Feb;6(3):57. doi: 10.21037/atm.2017.12.13. PMID: 29611546 CIN - Ann Transl Med. 2018 Feb;6(3):61. doi: 10.21037/atm.2017.12.27. PMID: 29611548 CIN - J Thorac Dis. 2018 Mar;10(3):1265-1268. doi: 10.21037/jtd.2018.03.28. PMID: 29708166 CIN - Transl Lung Cancer Res. 2018 Apr;7(Suppl 2):S165-S170. doi: 10.21037/tlcr.2018.03.19. PMID: 29782558 CIN - Transl Lung Cancer Res. 2018 Apr;7(Suppl 2):S127-S130. doi: 10.21037/tlcr.2018.03.06. PMID: 29782562 CIN - J Thorac Dis. 2018 Apr;10(Suppl 9):S1076-S1080. doi: 10.21037/jtd.2018.03.92. PMID: 29849216 CIN - Transl Lung Cancer Res. 2018 Sep;7(Suppl 3):S187-S190. doi: 10.21037/tlcr.2018.04.16. PMID: 30393597 CIN - J Thorac Dis. 2018 Nov;10(Suppl 33):S3837-S3839. doi: 10.21037/jtd.2018.09.52. PMID: 30631492 MH - Acrylamides MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality MH - Disease-Free Survival MH - Double-Blind Method MH - ErbB Receptors/*genetics MH - Erlotinib Hydrochloride/therapeutic use MH - Female MH - Gefitinib MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/genetics/mortality MH - Male MH - Middle Aged MH - *Mutation MH - Piperazines/adverse effects/*therapeutic use MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Protein-Tyrosine Kinases/antagonists & inhibitors MH - Quinazolines/therapeutic use MH - Survival Rate FIR - Boyer, Michael IR - Boyer M FIR - Lee, Chee IR - Lee C FIR - Hughes, Brett IR - Hughes B FIR - O'Byrne, Kenneth IR - O'Byrne K FIR - Briggs, Peter IR - Briggs P FIR - Milward, Michael IR - Milward M FIR - John, Thomas IR - John T FIR - Demedts, Ingel IR - Demedts I FIR - Bustin, Frederique IR - Bustin F FIR - Barrios, Carlos Henrique IR - Barrios CH FIR - Timcheva, Constanta IR - Timcheva C FIR - Butts, Charles IR - Butts C FIR - Goss, Glenwood IR - Goss G FIR - Juergens, Rosalyn IR - Juergens R FIR - Leighl, Natasha IR - Leighl N FIR - Cheng, Susanna IR - Cheng S FIR - Burkes, Ronald IR - Burkes R FIR - Zhang, Helong IR - Zhang H FIR - Shu, Yongqian IR - Shu Y FIR - Zhou, Qing IR - Zhou Q FIR - Li, Wei IR - Li W FIR - Feng, Guosheng IR - Feng G FIR - He, Yong IR - He Y FIR - Wang, Buhai IR - Wang B FIR - Gao, Hongjun IR - Gao H FIR - Nan, Kejun IR - Nan K FIR - Zhou, Xiangdong IR - Zhou X FIR - Fan, Yun IR - Fan Y FIR - Hunag, Jian an IR - Hunag JA FIR - Hu, Yi IR - Hu Y FIR - Liu, Yun-Peng IR - Liu YP FIR - Liu, Chunling IR - Liu C FIR - Zhang, Yiping IR - Zhang Y FIR - Zhu, Bo IR - Zhu B FIR - Bartek, Tomas IR - Bartek T FIR - Monnet, Isabelle IR - Monnet I FIR - El Kouri, Claude IR - El Kouri C FIR - Perol, Maurice IR - Perol M FIR - Berard, Henri IR - Berard H FIR - Madelaine, Jeannick IR - Madelaine J FIR - von Pawel, Joachim IR - von Pawel J FIR - Grohe, Christian IR - Grohe C FIR - Bohnet, Sabine IR - Bohnet S FIR - Bischoff, Helge IR - Bischoff H FIR - zum Buschenfelde, Christian Meyer IR - zum Buschenfelde CM FIR - Ruckert, Anja IR - Ruckert A FIR - Urban, Lazlo IR - Urban L FIR - Papi-Szekely, Zsolt IR - Papi-Szekely Z FIR - Csanky, Eszter IR - Csanky E FIR - Bocskei, Csaba IR - Bocskei C FIR - Tehenes, Sandor IR - Tehenes S FIR - Gottfried, Maya IR - Gottfried M FIR - Bar, Jair IR - Bar J FIR - Peled, Nir IR - Peled N FIR - Wollner, Mirjana IR - Wollner M FIR - Bertolini, Alessandro IR - Bertolini A FIR - Ardizzoia, Antonio IR - Ardizzoia A FIR - Accettura, Caterina IR - Accettura C FIR - Mitella, Michele IR - Mitella M FIR - Passalacqua, Rodolfo IR - Passalacqua R FIR - Novello, Silvia IR - Novello S FIR - Roila, Fausto IR - Roila F FIR - Tiseo, Marcello IR - Tiseo M FIR - Sekine, Akimasa IR - Sekine A FIR - Takahashi, Toshiaki IR - Takahashi T FIR - Kasahara, Kazuo IR - Kasahara K FIR - Yoh, Kiyotaka IR - Yoh K FIR - Sugawara, Shunichi IR - Sugawara S FIR - Kobayashi, Nobuaki IR - Kobayashi N FIR - Shimokawa, Tsuneo IR - Shimokawa T FIR - Okuda, Chiyuki IR - Okuda C FIR - Fukuhara, Tatsuo IR - Fukuhara T FIR - Sata, Masafumi IR - Sata M FIR - Nagakawa, Kazuhiko IR - Nagakawa K FIR - Atagi, Shinji IR - Atagi S FIR - Nakahara, Yoshiro IR - Nakahara Y FIR - Lee, Jong-Seok IR - Lee JS FIR - Lee, Kye Young IR - Lee KY FIR - Shin, Sang Won IR - Shin SW FIR - Kang, Jin-Hyoung IR - Kang JH FIR - How, Soon Hin IR - How SH FIR - Pang, Yong Kek IR - Pang YK FIR - Osorio-Sanchez, Jemela Anne IR - Osorio-Sanchez JA FIR - Ladrera, Guia Elena Imelda IR - Ladrera GEI FIR - Serwatowski, Piotr IR - Serwatowski P FIR - Szczesna, Aleksandra IR - Szczesna A FIR - Zajda, Katarzyna IR - Zajda K FIR - Ramlau, Rodryg IR - Ramlau R FIR - Sawka, Dariusz IR - Sawka D FIR - Encarnacao Teixeira, Maria IR - Encarnacao Teixeira M FIR - Almodovar, Teresa IR - Almodovar T FIR - Soares, Marta IR - Soares M FIR - Almeida, Amelia IR - Almeida A FIR - Barroso, Ana IR - Barroso A FIR - Schenker, Michael IR - Schenker M FIR - Girgorescu, Alexandru Calin IR - Girgorescu AC FIR - Iorga, Polixenia IR - Iorga P FIR - Orlov, Sergey IR - Orlov S FIR - Karaseva, Nina IR - Karaseva N FIR - Moiseenko, Vladimir IR - Moiseenko V FIR - Garcia Campelo, Rosario IR - Garcia Campelo R FIR - Isla Casado, Maria Dolores IR - Isla Casado MD FIR - Cobo Dols, Manuel IR - Cobo Dols M FIR - Nadal, Ernest IR - Nadal E FIR - Campayo Guillaumes, Marc IR - Campayo Guillaumes M FIR - Gonzalez Larriba, Jose Luis IR - Gonzalez Larriba JL FIR - Majem Tarruella, Margarita IR - Majem Tarruella M FIR - Vazquez Estevez, Sergio IR - Vazquez Estevez S FIR - Fuentes Pradera, Jose IR - Fuentes Pradera J FIR - Marquez Medina, Diego IR - Marquez Medina D FIR - Vikstrom, Anders IR - Vikstrom A FIR - Gautschi, Oliver IR - Gautschi O FIR - Britschgi, Christian IR - Britschgi C FIR - Mueller, Andreas IR - Mueller A FIR - Tsai, Ying-Huang IR - Tsai YH FIR - Wu, Ming-Fang IR - Wu MF FIR - Yang, Cheng-Ta IR - Yang CT FIR - Lin, Meng Chih IR - Lin MC FIR - Chen, Chao-Hsun IR - Chen CH FIR - Srimuninnimit, Vichien IR - Srimuninnimit V FIR - Laohavinij, Sudsawat IR - Laohavinij S FIR - Sriuranpong, Virote IR - Sriuranpong V FIR - Yildiz, Ramazan IR - Yildiz R FIR - Bondarenko, Igor IR - Bondarenko I FIR - Vynnychenko, Ihor IR - Vynnychenko I FIR - Adamchuk, Hryhoriy IR - Adamchuk H FIR - Shparyk, Yaroslav IR - Shparyk Y FIR - Price, Allan IR - Price A FIR - Summers, Yvonne IR - Summers Y FIR - Shah, Riyaz IR - Shah R FIR - Dragnev, Konstantin IR - Dragnev K FIR - Maniam, Ajit IR - Maniam A FIR - McCune, Steven IR - McCune S FIR - Ruiz, Jimmy IR - Ruiz J FIR - Janne, Pasi IR - Janne P FIR - Feinstein, Trevor IR - Feinstein T FIR - Hamm, John IR - Hamm J FIR - Anderson, Ian IR - Anderson I FIR - Khan, Farrah IR - Khan F FIR - Boccia, Ralph IR - Boccia R FIR - Tran, Ngoc IR - Tran N FIR - Nguyen, Nhung IR - Nguyen N EDAT- 2017/11/21 06:00 MHDA- 2018/01/19 06:00 CRDT- 2017/11/21 06:00 PHST- 2017/11/21 06:00 [pubmed] PHST- 2018/01/19 06:00 [medline] PHST- 2017/11/21 06:00 [entrez] AID - 10.1056/NEJMoa1713137 [doi] PST - ppublish SO - N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.