• David Planchard, Michael J Boyer, Jong-Seok Lee, Arunee Dechaphunkul, Parneet K Cheema, Toshiaki Takahashi, Jhanelle E Gray, Marcello Tiseo, Suresh S Ramalingam, Alexander Todd, Astrid McKeown, Yuri Rukazenkov, and Yuichiro Ohe.
• Department of Medical Oncology, Gustave Roussy, Villejuif, France. david.planchard@gustaveroussy.fr.
• Clin Cancer Res. 2019 Apr 1; 25 (7): 2058-2063.

PurposeIn 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 MethodsPatients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (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 independently confirmed objective disease progression with documented postprogression T790M-positive mutation status.ResultsAt 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].ConclusionsAll postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.©2019 American Association for Cancer Research.

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