Osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC): FLAURA Asian subset

Abstract

Background: Osimertinib is a 3r generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFRm and EGFR T790M resistance mutations. 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. We present results of an Asian subset (Asian pts enrolled at Asian sites) of FLAURA. Method(s): Eligible pts: > 18 yrs (Japan: >20 yrs), 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 cutoff: 12 June 2017. Result(s): 322 Asian pts (Chinese n = 46, Japanese n = 120, other Asian n = 156) received treatment. Baseline characteristics were generally balanced across arms. PFS benefit was broadly consistent across predefined subgroups (HR ranging from 0.48-0.68). Median total treatment duration (range): 15.5 (0.5-25.5) mo with osimertinib; 11.7 (0-26.2) with SoC. All causality adverse events (AEs), by investigator: osimertinib, 99% (Gr > 3, 40%); SoC, 99% (Gr > 3, 48%). AEs leading to discontinuation: osimertinib, 15%; SoC, 21%. Most common all causality AEs with osimertinib: diar-rhoea(54% [Gr> 3, 2%]), paronychia (40% [1%]);SoC: diarrhoea(54% [3%]), dermatitis acneiform (53% [6%]). Conclusion(s): Results in Asian pts with EGFRm advanced NSCLC were consistent with the overall results of the FLAURA study. First-line osimertinib demonstrated superior efficacy over SoC. There were no new safety findings. Clinical trial identification: NCT02296125.