Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis

Date 28 September 2019
Event ESMO 2019 Congress
Session Presidential Symposium I
Topics Non-Small Cell Lung Cancer
Presenter Suresh Ramalingam
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors S.S. Ramalingam1, J.E. Gray2, Y. Ohe3, B.C. Cho4, J. Vansteenkiste5, C. Zhou6, T. Reungwetwattana7, Y. Cheng8, B. Chewaskulyong9, R. Shah10, K.H. Lee11, P. Cheema12, M. Tiseo13, T. John14, M.C. Lin15, F. Imamura16, R. Hodge17, Y. Rukazenkov18, J. Soria19, D. Planchard20
  • 1Hematology And Medical Oncology, Emory University, Winship Cancer Institute, 30322 - Atlanta/US
  • 2Department Of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 3Department Of Internal Medicine, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 4Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 5Oncology, University Hospital KU Leuven, Leuven/BE
  • 6Oncology, Pulmonary Hospital of Tongji University, Shanghai/CN
  • 7Faculty Of Medicine, Ramathibodi Hospital, Mahidol University, 10400 - Bangkok/TH
  • 8Department Of Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun/CN
  • 9Oncology Unit, Department Of Medicine, Chiang Mai University, Chiang Mai/TH
  • 10Oncology, Kent Oncology Centre, Maidstone Hospital, Maidstone and Tunbridge Wells NHS Trust, Maidstone/GB
  • 11Division Of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, 361-711 - Cheongju/KR
  • 12William Osler Health System, University of Toronto, Toronto/CA
  • 13Medical Oncology Unit, University Hospital of Parma, 43126 - Parma/IT
  • 14Department Of Medical Oncology, Austin Health, Melbourne/AU
  • 15Division Of Pulmonary And Critical Care Medicine, Department Of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital.Chang Gung University College of Medicine, Kaohsiung/TW
  • 16Department Of Thoracic Oncology, Osaka International Cancer Institution, 537-8511 - Osaka/JP
  • 17Oncology R&d, AstraZeneca, CB4 0WG - Cambridge/GB
  • 18Oncology R&d, AstraZeneca, Cambridge/GB
  • 19Early Oncology, Research & Development, AstraZeneca and Université Paris-Sud, Orsay, France, 20878 - Gaithersburg/US
  • 20Department Of Medical Oncology, Gustave Roussy, 94800 - Villejuif/FR



Osimertinib is a 3rd-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-mutated (EGFRm) and EGFR T790M resistance mutations, and has demonstrated efficacy in NSCLC CNS metastases. In the phase III FLAURA study (NCT02296125), osimertinib resulted in significant progression-free survival (PFS) benefit (primary endpoint; datacut off [DCO] 12 June 2017) over comparator EGFR-TKI (HR 0.46, p < 0.001). Overall survival (OS) data were immature (25% maturity) at that time. Here, we report the final OS analysis (58% maturity).


Eligible patients (pts): ≥18 years (Japan: ≥20), treatment-naïve with Ex19del/L858R EGFRm advanced NSCLC; WHO performance status 0–1. Pts with stable CNS metastases not requiring steroids for ≥2 weeks were allowed. Pts were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (gefitinib 250 mg qd/erlotinib 150 mg qd po), stratified by mutation status (Ex19del/L858R) and race (Asian/non-Asian). Crossover was allowed for pts in the comparator EGFR-TKI arm upon central confirmation of progression and T790M positivity. Primary endpoint: PFS by RECIST v1.1, per investigator. OS was a secondary endpoint. DCO 25 June 2019.


Globally, 556 pts were randomised to osimertinib (n = 279) or comparator EGFR-TKI (n = 277). Per study protocol, 70 (25%) pts crossed over from comparator EGFR-TKI to osimertinib. Osimertinib significantly improved OS vs comparator EGFR-TKI. All causality AEs, per investigator: osimertinib, 98% (grade ≥3, 42%); comparator EGFR-TKI, 98% (grade ≥3, 47%). AEs leading to discontinuation: osimertinib, 15%; comparator EGFR-TKI, 18%. The safety profile appears consistent with previously reported data.Table:


Efficacy outputOsimertinib n = 279Comparator EGFR-TKI n = 277
OS hazard ratio0.799 (0.641, 0.997); p = 0.0462
(95.05% confidence interval)
Median OS, months38.631.8
(95% confidence interval)(34.5, 41.8)(26.6, 36.0)
Deaths, total pts (%)155 (56)166 (60)
Median follow-up for OS in all pts, months35.827.0
Median follow-up for OS in censored* pts, months43.143.1
12-month survival rate, %8983
(95% confidence interval)(85, 92)(77, 87)
24-month survival rate, %7459
(95% confidence interval)(69, 79)(53, 65)
36-month survival rate, %5444
(95% confidence interval)(48, 60)(38, 50)

OS for patients in the full analysis set was analysed using a log rank test (stratified by race and mutation type) for generation of the p-value and using the Breslow approach for handling ties. The median OS with 95% confidence intervals were calculated by Kaplan Meier technique. For statistical significance, a 2-sided p-value of less than 0.0495, as determined by the O’Brien-Fleming approach was required due the previous interim analysis.*Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive.


Osimertinib provided a statistically significant and clinically meaningful improvement in OS vs comparator EGFR-TKI in first-line pts with EGFRm advanced NSCLC.

Clinical trial identification


Editorial acknowledgement

Natalie Griffiths, PhD, from iMed Comms, an Ashfield Company; funded by AstraZeneca.

Legal entity responsible for the study





S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda. J.E. Gray: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Takeda; Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Celgene, Takeda; Research grant / Funding (institution): Array, Merck, AstraZeneca, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca, Chugai, Dainippon Lilly, Ono, BMS Japan, Daiichi Sankyo, BI, Bayer, Ignyta, Pfizer, MSD, Taiho, Novartis, Kyorin, Kyowa Hakko Kirin, Takeda, Celltrion, Kissei, Amgen, Janssen, ROXO. B.C. Cho: Honoraria (institution), Advisory / Consultancy: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Eli Lilly, Takeda; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Licensing / Royalties: Champions Oncology; Shareholder / Stockholder / Stock options: TheraCanVac Inc.. J. Vansteenkiste: Research grant / Funding (institution): MSD; Advisory / Consultancy: Apotex, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Roche; Speaker Bureau / Expert testimony: AstraZeneca, BMS, MSD, Roche. C. Zhou: Honoraria (self): Roche, Eli Lilly, Boehringer Ingelheim, Merck, Hengrui and Qiru. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. R. Shah: Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim, Roche, AstraZeneca. P. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Merck, Takeda, Novartis, Genomic Health, Pfizer. M. Tiseo: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, Takeda; Research grant / Funding (institution): AstraZeneca. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. F. Imamura: Honoraria (self), Research grant / Funding (institution): AstraZeneca. R. Hodge: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Advisory / Consultancy: AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, and Takeda; Shareholder / Stockholder / Stock options: AstraZeneca, Gritstone; Full / Part-time employment: AstraZeneca. D. Planchard: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel / Accommodation / Expenses: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim , Roche, Merck,Novartis, prIME Oncology, Pfizer. All other authors have declared no conflicts of interest.