Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study

• Type of Material: Article
• Authors: Ying Cheng, Jilin Provincial Cancer Hospital; Yong He, Daping Hospital China; We Li, First Hospital of Jilin University; He-Long Zhang, Fourth Military Medical University; Qing Zhou, Guangdong Provincial People’s Hospital; Buhai Wang, Yangzhou University; Chunling Liu, Xinjiang Medical University; Andrew Walding, AstraZeneca, Cambridge, UK; Matilde Saggese, AstraZeneca, Cambridge, UK; Xiangning Huang, AstraZeneca, Cambridge, UK; Minhao Fan, AstraZeneca, Cambridge, UK; Jia Wang, AstraZeneca, Cambridge, UK; Suresh Ramalingam, Emory University
• Language: English
• Date: 2021-02-05
• Publisher: SPRINGER
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s11523-021-00794-6
• Title of Journal or Parent Work: TARGETED ONCOLOGY
• Volume: 16
• Issue: 2
• Start Page: 165
• End Page: 176
• Grant/Funding Information: The study (NCT02296125) was funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib. AstraZeneca was involved in the study design; the collection, analysis, and interpretation of data; the writing of this article; and its approval for submission.
• Keywords: OPEN-LABEL; GEMCITABINE/CISPLATIN; CELL LUNG-CANCER; DACOMITINIB; Life Sciences & Biomedicine; MUTATIONS; ERLOTINIB; GEFITINIB; CHEMOTHERAPY; AFATINIB; Science & Technology; PHASE-III; Oncology
• Research Categories: Health Sciences, Public Health; Health Sciences, Oncology

Abstract

Background: In the global FLAURA study, first-line osimertinib, a third-generation irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), significantly improved progression-free survival (PFS) and overall survival (OS) versus comparator EGFR TKIs in patients with EGFR mutation-positive (EGFRm) advanced non-small-cell lung cancer (NSCLC). Objective: The FLAURA China study assessed first-line osimertinib in Chinese patients with EGFRm advanced NSCLC (NCT02296125). Methods: FLAURA China was a double-blind, randomized, phase III study. Adults from mainland China with previously untreated EGFRm (Exon 19 deletion or L858R) advanced NSCLC were enrolled in the global study or a China-only study under the same protocol; 136 patients were randomized to osimertinib (80 mg once daily [od]; n = 71) or comparator EGFR TKI (gefitinib or erlotinib; all sites selected gefitinib 250 mg od; n = 65). Patients were randomized and allocated to treatment groups by a central computer system. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint. Results: All 136 randomized patients were analyzed. Osimertinib extended median PFS by 8.0 months versus comparator EGFR TKI (17.8 vs. 9.8 months; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.37–0.85). Median OS was 33.1 months in the osimertinib group versus 25.7 months in the comparator group (HR 0.85; 95% CI 0.56–1.29). At 3 years, 20% of patients on osimertinib and 8% on the comparator remained on randomized treatment. Grade 3 or higher adverse events (AEs) were reported in 54 and 28% of patients in the osimertinib and comparator groups, respectively, driven by increased local reporting of laboratory- and disease-related AEs. No new safety signals were identified. Conclusions: First-line osimertinib treatment resulted in a clinically meaningful PFS and OS benefit versus comparator EGFR TKI in Chinese patients with EGFRm advanced NSCLC. Safety data were consistent with the known safety profile of osimertinib. Clinical Trial Registration: ClinicalTrials.gov NCT02296125, registered 20 November 2014.