Osimertinib (osi) after definitive chemoradiotherapy (CRT) in unresectable stage III epidermal growth factor receptor-mutated (EGFRm) NSCLC: LAURA China cohort analysis

BackgroundIn Chinese patients (pts) with NSCLC, incidence of EGFRm disease is high (∼35–50%). Osi is a 3rd-generation, oral EGFR-TKI recommended for EGFRm advanced NSCLC and as adjuvant therapy for resected EGFRm NSCLC. LAURA (NCT03521154) is a global, phase III, double-blind, placebo (PBO)-controlled study evaluating the efficacy/safety of osi in unresectable stage III EGFRm NSCLC without progression after definitive CRT. In LAURA, osi showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS). We report pre-specified, exploratory analyses of efficacy/safety in Chinese pts in LAURA.MethodsEligible pts: ≥18 yrs, WHO PS 0/1, unresectable stage III EGFRm (Ex19del/L858R) NSCLC, had received definitive platinum-based CRT with no progression. Pts were randomised 2:1 to receive osi 80 mg or PBO QD until blinded independent central review (BICR)-confirmed progression/discontinuation. Imaging, including brain MRI, was performed at baseline, every 8 wks to wk 48, then every 12 wks until progression by BICR. Open-label osi was offered post-progression. Primary endpoint: BICR-assessed PFS; secondary endpoints included overall survival (OS) and safety. Data cut-off: 5 Jan 2024.ResultsOf 216 pts randomised globally, 40 (19%) were Chinese (osi n=27; PBO n=13). Baseline characteristics were generally balanced between arms and consistent with the global population. Median PFS by BICR was not reached (95% CI 17.4 mos, not calculable) for osi vs 3.7 mos (1.8, 7.7) for PBO. PFS rate for osi vs PBO was 80% vs 17% at 12 mos and 71% vs 8% at 24 mos. Investigator-assessed PFS was consistent with BICR assessment. OS data were immature (2 events per arm). All-causality AEs occurred in 96% vs 77% pts; grade [G] ≥3 AEs in 30% vs 8%; serious AEs in 41% vs 23%; any AEs leading to discontinuation in 15% vs 8% for osi vs PBO, respectively. Radiation pneumonitis (grouped term) occurred in 52% vs 38% pts for osi vs PBO; most G1/2.ConclusionsClinical benefit/safety with osi in Chinese pts in LAURA were consistent with the global population, supporting osi after definitive CRT as the new standard of care globally and for Chinese pts with unresectable stage III EGFRm NSCLC.Clinical trial identificationNCT03521154; EudraCT number: 2018-001061-16.Editorial acknowledgementThe authors would like to acknowledge Caroline Allinson contracted by Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines.Legal entity responsible for the studyAstraZeneca.FundingAstraZeneca.DisclosureY. Pan: Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, MSD, Pfizer, Roche. E. Armenteros Monterroso, J. Liu, W. Fu, Y. Zhao: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca. X. Huang: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Personal and Institutional, Stocks or ownership: AstraZeneca. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Novartis, Yuhan Corporation, Menarini, Mirati Therapeutics Inc, Daiichi Sankyo, Inc, D3 Bio Limited, Simcere, Takeda, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Member of Board of Directors: Innovent biologics, inc; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui Beigene, Roche, Hansoh; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh. All other authors have declared no conflicts of interest.