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

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.

Conflict of interest statement

YC, WL, HZ, and CL have no conflicts of interest that are directly relevant to the content of this article. YH has received personal fees from AstraZeneca, Eli Lilly, Pfizer, and Roche for speaker bureau/expert testimony. QZ has received personal honoraria from AstraZeneca and Roche. BW has received personal fees from AstraZeneca, Boehringer Ingelheim, and Roche for advisory/consultancy and speaker bureau/expert testimony and from Eli Lilly for speaker bureau/expert testimony. AW, MS, and XH are employees and shareholders/stockholders of and hold stock options for AstraZeneca. MF received personal fees from AstraZeneca during the conduct of the study and is an employee of AstraZeneca. JW is an employee of AstraZeneca. SSR has received grants and personal fees from Amgen, BMS, Merck, Tesaro, and Takeda; grants from Advaxis and Genmab; grants, personal fees, and non-financial support from AstraZeneca; and personal fees from Genentech and Glaxo Smith Kline, outside the submitted work.

Figures

Fig. 1

Kaplan–Meier plots of a investigator-assessed progression-free survival and b overall survival (full analysis set). Censored data are indicated by tick marks. Data from patients who had not died at the time of the analysis were censored on the basis of the last recorded date on which the patient was known to be alive. CI confidence interval, EGFR TKI epidermal growth factor receptor tyrosine kinase inhibitor, OS overall survival, PFS progression-free survival

Fig. 2

Subgroup analyses of a investigator-assessed progression-free survival and b overall survival (full analysis set). This analysis was performed using a Cox proportional hazards model, including treatment, subgroup, and a treatment-by-subgroup interaction term. Subgroup categories with < 20 events were excluded from the analysis. A hazard ratio of <1.00 indicates a lower risk of death with osimertinib than with the comparator EGFR TKI. CI confidence interval, CNS central nervous system, EGFR epidermal growth factor receptor, HR hazard ratio, NS not calculable, OS overall survival, PFS progression-free survival, PH proportional hazards, TKI tyrosine kinase inhibitor, WHO World Health Organization. *EGFR mutation is by method used at randomization

Fig. 3

a First and b second subsequent anticancer therapies received (full analysis set). The first/second subsequent anticancer therapy is the first/second treatment started on or after the last dose date of randomized study treatment. 2L second line, 3L third line, EGFR epidermal growth factor receptor, FST first subsequent therapy, SST second subsequent therapy, TKI tyrosine kinase inhibitor. *Other therapy refers to patients who did not receive either chemotherapy or an EGFR TKI