Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) 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. Methods: 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 80mg once daily (qd) orally (po) or SoC EGFR‐TKI (gefitinib 250mg or erlotinib 150mg qd po), stratified by mutation status (Ex19del/L858R) and race (Asian/non‐Asian). Primary endpoint: progressionfree survival (PFS) by RECIST v1.1, by investigator. Data cut‐off: 12 June 2017. Results: 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% (Gr≥3, 34%); SoC, 98% (Gr≥3, 45%). AEs leading to discontinuation: osimertinib, 13%; SoC, 18%. Most common all causality AEs with osimertinib: diarrhoea (58% [Gr≥3, 2%]), dry skin (32% [<1%]); SoC: diarrhoea (57% [3%]), dermatitis acneiform (48% [5%]). Conclusions: Osimertinib demonstrated a superior risk/benefit over SoC as first‐line therapy in pts with advanced EGFRm NSCLC. (Table Presented).