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

Abstract

Purpose: Osimertinib, a 3rd generation, irreversible, oral EGFR-TKI potently and selectively inhibits both EGFRm and EGFR T790M and has demonstrated efficacy in NSCLC CNS metastases. The phase III FLAURA study (NCT02296125) compared 1st line osimertinib vs comparator EGFR-TKI in EGFRm advanced NSCLC. Median progression-free survival (PFS; primary analysis, DCO 06/12/2017) was significantly longer with osimertinib than comparator EGFR-TKI (18.9 vs 10.2 months; p<0.001). Overall survival (OS) data were immature (25% maturity) at the time of the primary publication. Method(s): Patients (pts; 556 globally) were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (gefitinib 250 mg qd or erlotinib 150 mg qd po) and stratified by race (Asian/non-Asian) and mutation status (Ex19del/L858R). Inclusion criteria: >=18 years (Japan: >=20); treatment-naive with Ex19del/L858R EGFRm advanced NSCLC; WHO PS 0-1; neurologically stable pts with CNS metastases were allowed, provided definitive treatment/steroids were completed for >=2 weeks. Treatment beyond progression (RECIST 1.1, per investigator) was allowed if clinical benefit continued; pts randomised to the comparator arm could crossover to osimertinib if T790M positive on progression (BICR confirmed). Primary endpoint: PFS by RECIST 1.1, per investigator. OS is a secondary endpoint. Safety and tolerability measures included adverse events (CTCAE v4), clinical and physical assessments. Result(s): The data for final OS analysis (app. 60% maturity across both arms) is anticipated by 08/2019. At ESMO 2019 median OS, 2-and 3-year survival rates will be reported for each arm as well as OS across predefined subgroups including race and EGFR mutation type as well as updated safety data. We will for the first time provide FLAURA data on the prevalence of T790M mutations in different molecular subgroups (Ex19del/ L858R) after progression on 1st line EGFR-TKI. Conclusion(s): Not applicable.