Osimertinib vs standard of care EGFR-TKI as first-line treatment in patients with EGFRm advanced NSCLC: FLAURA

Abstract

Background: 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. Method(s): 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. Result(s): 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%. PFS benefit was consistent across all subgroups, including pts with/without CNS mets at study entry. Median total treatment duration (range): 16.2 (0.1-27.4) months with osimertinib; 11.5 (0-26.2) with SoC. All causality adverse events (AEs), by investigator: osimertinib, 98% (Gr3, 34%); SoC, 98% (Gr3, 45%). AEs leading to discontinuation: osimertinib, 13%; SoC, 18%. Most common all causality AEs with osimertinib: diarrhoea (58% [Gr3, 2%]), dry skin (32% [<1%]); SoC: diarrhoea (57% [3%]), dermatitis acneiform (48% [5%]). Conclusion(s): Osimertinib demonstrated a superior risk/benefit over SoC as first-line therapy in pts with advanced EGFRm NSCLC.