PMID- 33544337 OWN - NLM STAT- MEDLINE DCOM- 20211101 LR - 20220603 IS - 1776-260X (Electronic) IS - 1776-2596 (Print) IS - 1776-2596 (Linking) VI - 16 IP - 2 DP - 2021 Mar TI - Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. PG - 165-176 LID - 10.1007/s11523-021-00794-6 [doi] AB - BACKGROUND: In the global FLAURA study, first-line osimertinib, a third-generation irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), significantly improved progression-free survival (PFS) and overall survival (OS) versus comparator EGFR TKIs in patients with EGFR mutation-positive (EGFRm) advanced non-small-cell lung cancer (NSCLC). OBJECTIVE: The FLAURA China study assessed first-line osimertinib in Chinese patients with EGFRm advanced NSCLC (NCT02296125). METHODS: FLAURA China was a double-blind, randomized, phase III study. Adults from mainland China with previously untreated EGFRm (Exon 19 deletion or L858R) advanced NSCLC were enrolled in the global study or a China-only study under the same protocol; 136 patients were randomized to osimertinib (80 mg once daily [od]; n = 71) or comparator EGFR TKI (gefitinib or erlotinib; all sites selected gefitinib 250 mg od; n = 65). Patients were randomized and allocated to treatment groups by a central computer system. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint. RESULTS: All 136 randomized patients were analyzed. Osimertinib extended median PFS by 8.0 months versus comparator EGFR TKI (17.8 vs. 9.8 months; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.37-0.85). Median OS was 33.1 months in the osimertinib group versus 25.7 months in the comparator group (HR 0.85; 95% CI 0.56-1.29). At 3 years, 20% of patients on osimertinib and 8% on the comparator remained on randomized treatment. Grade 3 or higher adverse events (AEs) were reported in 54 and 28% of patients in the osimertinib and comparator groups, respectively, driven by increased local reporting of laboratory- and disease-related AEs. No new safety signals were identified. CONCLUSIONS: First-line osimertinib treatment resulted in a clinically meaningful PFS and OS benefit versus comparator EGFR TKI in Chinese patients with EGFRm advanced NSCLC. Safety data were consistent with the known safety profile of osimertinib. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02296125, registered 20 November 2014. FAU - Cheng, Ying AU - Cheng Y AUID- ORCID: 0000-0001-9908-597X AD - Department of Medical Oncology, Jilin Provincial Cancer Hospital, Changchun, 130000, China. jl.cheng@163.com. FAU - He, Yong AU - He Y AD - Respiratory Disease, Daping Hospital, Chongqing, China. FAU - Li, Wei AU - Li W AD - The First Hospital of Jilin University, Changchun, Jilin, China. FAU - Zhang, He-Long AU - Zhang HL AD - Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China. FAU - Zhou, Qing AU - Zhou Q AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Wang, Buhai AU - Wang B AD - Department of Oncology of Subei People's Hospital, Yangzhou University, Yangzhou, Jiangsu, China. FAU - Liu, Chunling AU - Liu C AD - Tumor Hospital, Xinjiang Medical University, Urumqi, China. FAU - Walding, Andrew AU - Walding A AD - Global Medicines Development, GMED Oncology, AstraZeneca, Cambridge, UK. FAU - Saggese, Matilde AU - Saggese M AD - Global Medicines Development, GMED Oncology, AstraZeneca, Cambridge, UK. FAU - Huang, Xiangning AU - Huang X AD - Global Medicines Development, GMED Oncology, AstraZeneca, Cambridge, UK. FAU - Fan, Minhao AU - Fan M AD - Global Medicines Development, AstraZeneca, Shanghai, China. FAU - Wang, Jia AU - Wang J AD - Global Medicines Development, AstraZeneca, Shanghai, China. FAU - Ramalingam, Suresh S AU - Ramalingam SS AD - Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. LA - eng SI - ClinicalTrials.gov/NCT02296125 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210205 PL - France TA - Target Oncol JT - Targeted oncology JID - 101270595 RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 0 (Protein Kinase Inhibitors) RN - 3C06JJ0Z2O (osimertinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Acrylamides/pharmacology/*therapeutic use MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds/pharmacology/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - China MH - Double-Blind Method MH - ErbB Receptors/metabolism MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Mutation MH - Protein Kinase Inhibitors/pharmacology/*therapeutic use PMC - PMC7935816 COIS- YC, WL, HZ, and CL have no conflicts of interest that are directly relevant to the content of this article. YH has received personal fees from AstraZeneca, Eli Lilly, Pfizer, and Roche for speaker bureau/expert testimony. QZ has received personal honoraria from AstraZeneca and Roche. BW has received personal fees from AstraZeneca, Boehringer Ingelheim, and Roche for advisory/consultancy and speaker bureau/expert testimony and from Eli Lilly for speaker bureau/expert testimony. AW, MS, and XH are employees and shareholders/stockholders of and hold stock options for AstraZeneca. MF received personal fees from AstraZeneca during the conduct of the study and is an employee of AstraZeneca. JW is an employee of AstraZeneca. SSR has received grants and personal fees from Amgen, BMS, Merck, Tesaro, and Takeda; grants from Advaxis and Genmab; grants, personal fees, and non-financial support from AstraZeneca; and personal fees from Genentech and Glaxo Smith Kline, outside the submitted work. EDAT- 2021/02/06 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/02/05 CRDT- 2021/02/05 12:15 PHST- 2021/01/27 00:00 [accepted] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/02/05 12:15 [entrez] PHST- 2021/02/05 00:00 [pmc-release] AID - 10.1007/s11523-021-00794-6 [pii] AID - 794 [pii] AID - 10.1007/s11523-021-00794-6 [doi] PST - ppublish SO - Target Oncol. 2021 Mar;16(2):165-176. doi: 10.1007/s11523-021-00794-6. Epub 2021 Feb 5.