Post-Progression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-Mutated Advanced Non-Small Cell Lung Cancer.

Purpose:In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non-small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25%). Here we report exploratory postprogression outcomes. Patients and Methods:Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFRTKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after indepen-dently confirmed objective disease progression with documented postprogression T790M-positive mutation status. Results:At data cutoff (June 12, 2017), 138 of 279 (49%) and 213 of 277 (77%) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59%) and 129 (61%), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95% confidence interval (CI), 19.5-not calculable (NC)] in the osimertinib arm and 16.0 months (95% CI, 14.8-18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95% CI, 23.7-NC) in the osimertinib arm and 20.0 months (95% CI, 18.2-NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95% CI, 0.44-0.78; P = 0.0004]. Conclusions:All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.