Abstract 1295P
Background
In the phase III FLAURA study (NCT02296125), osimertinib significantly improved OS vs comparator EGFR-TKI (gefitinib/erlotinib) in treatment-naïve patients (pts) with EGFRm advanced NSCLC; OS hazard ratio (HR) 0.799, p=0.0462. In the FLAURA China study, osimertinib improved PFS vs comparator (HR 0.56, p=0.007); here we report OS in these pts.
Methods
A cohort of Chinese pts were enrolled separately from the global study under the same protocol. Eligible pts: ≥18 years, treatment-naïve EGFRm advanced NSCLC; WHO performance status (PS) 0–1. Pts were randomised 1:1 to osimertinib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (all Chinese pts received gefitinib 250 mg qd po), and stratified by race (Asian/non-Asian) and mutation status (Ex19del/L858R). Note all pts in the FLAURA China cohort were in the stratum of Asian. Pts in the comparator EGFR-TKI arm could cross over upon confirmation of progression and T790M positivity. OS was a secondary endpoint. Data cut-off: 25 June 2019.
Results
136 pts were randomised (osimertinib n=71; comparator EGFR-TKI n=65); 19 of these pts were included in the global analysis. Baseline characteristics were balanced across arms; WHO PS of 1: ≥80% in both arms. The median OS was 33.1 months for osimertinib compared with 25.7 months for the comparator arm (HR 0.848; Table). In the comparator arm, 22/65 pts (34%) crossed over to osimertinib. In the osimertinib and comparator arms, respectively, all causality adverse events (AEs) were reported in 99% and 98% of pts, grade ≥3 AEs: 54% and 28%, and AE leading to discontinuation: 13% and 6%. No new safety signals were identified. Table: 1295P
| Osimertinib n=71 | Comparator EGFR-TKI n=65 | |
| Median follow-up for OS*, mo | 31.0 | 24.9 |
| Deaths, n (%) | 45 (63) | 44 (68) |
| Median OS, mo (95% CI) | 33.1 (26.0, 35.9) | 25.7 (19.6, 32.8) |
| OS HR (95% CI) # | 0.848 (0.557, 1.291) | |
| Survival rate, % (95% CI)12 mo 24 mo 36 mo | 83 (72, 90) 64 (52, 74) 39 (27, 50) | 81 (70, 89) 54 (41, 66) 33 (21, 44) |
| Median actual treatment duration, mo | 20.0 | 13.6 |
| Median TFST, mo (95% CI) | 21.4 (18.8, 27.4) | 15.8 (11.9, 20.0) |
| TFST HR (95% CI) | 0.623 (0.424, 0.916) | |
| Median TSST, mo (95% CI) | 29.6 (23.1, 33.9) | 22.1 (17.4, 28.8) |
| TSST HR (95% CI) | 0.785 (0.525, 1.175) |
*All pts.#This analysis was not powered for OS.CI, confidence interval; mo, months; TFST/TSST, time to first/second subsequent therapy or death.
Conclusions
In the FLAURA China study, median OS was extended by 7.4 months in the osimertinib arm vs comparator EGFR-TKI arm in the first-line treatment of pts with EGFRm advanced NSCLC, consistent with the global population where osimertinib extended OS by 6.8 months. Safety data were comparable with the global population.
Clinical trial identification
NCT02296125.
Editorial acknowledgement
We thank Natalie Griffiths, PhD, from iMed Comms, who provided medical writing support funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
Y. He: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Eli Lilly. Q. Zhou: Honoraria (self): Roche; Honoraria (self): AstraZeneca. B. Wang: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Eli Lilly. A. Walding, M. Saggese, X. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. Y. Liu, R. Su: Full/Part-time employment: AstraZeneca. S.S. Ramalingam: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): Genmab. All other authors have declared no conflicts of interest. https://doi.org/10.1016/j.annonc.2020.08.1609