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

Introduction: 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 NSCLC. Interim overall survival data were encouraging but not formally statistically significant at current maturity (25%). Here we report exploratory post-progression outcomes. Methods: Patients were randomized 1:1 to receive osimertinib (80 mg orally [po], once daily [qd]) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, po, qd). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could crossover to receive osimertinib after independently confirmed objective disease progression with documented post-progression T790M-positive mutation status. Results: At data cutoff (June 12, 2017), 138/279 (49%) and 213/277 (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% 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 (HR, 0.58; 95% CI, 0.44-0.78; P = 0.0004). Conclusion: All post-progression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim overall survival data.

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