Osimertinib is a third-generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFRm and EGFR T790M resistance mutations. Pre- and early clinical data suggest osimertinib may also be effective as initial therapy for EGFRm advanced NSCLC. FLAURA (NCT02296125) is a PhIII, double-blind, randomised study assessing efficacy and safety of osimertinib vs SoC EGFR-TKI in first-line pts with EGFRm advanced NSCLC.
Eligible pts: ≥18 years, no prior EGFR-TKI/systemic anti-cancer therapy for advanced disease, with Ex19del/L858R EGFRm advanced NSCLC. Neurologically stable pts with CNS mets were allowed, provided definitive treatment/steroids were completed for ≥2 weeks. Pts were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg qd po), stratified by mutation status (Ex19del/L858R) and race (Asian/non-Asian). Primary endpoint: progression-free survival (PFS) by RECIST v1.1, by investigator. Data cut-off: 12 June 2017.
Globally, 556 pts were randomised to treatment. Baseline characteristics were balanced across arms (osimertinib/SoC): female 64/62%; Asian 62/62%, Ex19del 57/56%, L858R 35/32%, CNS mets 19/23%.Table:
|n = 279||n = 277|
|PFS hazard ratio (HR)||0.46 (0.37, 0.57); p |
Osimertinib demonstrated a superior risk/benefit over SoC as first-line therapy in pts with advanced EGFRm NSCLC.
Clinical trial identification
Legal entity responsible for the study
S. Ramalingam: Advisory Board Meeting for: Astra Zeneca, Bristol-Myers Squibb, Genentech, Boehringer-Ingelheim. F. Imamura: Research fund and honoraria from AstraZeneca. N. Nogami: Funding from AstraZeneca. Y. Ohe: Honorarium/Consultant/Expert Testimony/Research Funding (Institution); AstraZeneca, Chugai, Lilly, ONO, BMS, Daiichi-Sankyo, Nippon Kayaku, Boehringer, Bayer, Pfizer, MSD, Taiho, Clovis, Sanofi, Novartis, Kyorin, Dainippon-Sumitomo, Merck. J.F. Vansteenkiste: Grants/research support: AstraZeneca Honoraria/consultation fees: AstraZeneca, Novartis, MSD, Boehringer-Ingelheim, Eli-Lilly, Roche. C. Zhou: Lecture honorarium: Eli Lily, AstraZeneca, Roche, Pfizer, Sanofi, Boehringer-Ingelheim, Henrui Advisory Board: Roche, Boehringer-Ingelheim, AstraZeneca. J. Gray: Consultant/Advisory Boards: AstraZeneca, Celgene, Eli Lilly, Janssen, Boehringer-Ingelheim, Clovis. Research Funding: Array, AstraZeneca, Merck, Trovagene. R. Hodge, Y. Rukazenkov: Employee of, and shareholder in, AstraZeneca. J-C. Soria: Consultancy fees for AstraZeneca, Roche. All other authors have declared no conflicts of interest.