LBA4 - Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable (UR) stage III EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC): Updated overall survival (OS) analysis from the LAURA study

Background

In the double-blind Phase III LAURA study (NCT03521154), treatment (tx) with osi, a 3rd-generation, CNS-active EGFR-TKI, after definitive CRT significantly improved progression-free survival (PFS) vs placebo (pbo) in pts with UR stage III EGFRm NSCLC (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10, 0.24; p

Methods

Following definitive concurrent or sequential platinum-based CRT, adult pts with UR stage III EGFRm (Ex19del/L858R) NSCLC were randomised 2:1 to receive osi 80 mg QD or pbo until disease progression/discontinuation. Open-label osi was offered to pts in both tx arms post-progression. Primary endpoint: PFS by blinded independent central review per RECIST 1.1. OS was a key secondary endpoint. Updated OS is presented from a data cut-off (DCO) of 29 Nov 2024.

Results

All randomised pts received study tx (osi n=143; pbo n=73). At DCO, 74 (52%) vs 69 (95%) pts had discontinued study tx with osi vs pbo, respectively, of whom 54 (73%) vs 60 (87%) received subsequent tx. The most common types of subsequent tx (in any line) were an EGFR-TKI, received by 37 (50%) pts in the osi arm vs 60 (87%) in the pbo arm, cytotoxic chemotherapy, received by 28 (38%) vs 15 (22%), respectively, and radiotherapy, received by 28 (38%) vs 7 (10%) pts, respectively. At DCO, 40 (28%) pts in the osi arm and 26 (36%) in the pbo arm had died. Compared with the interim analysis, there was an improved trend towards OS benefit (maturity 31%) with osi vs pbo (median OS 58.8 months [95% CI 54.1, not calculable (NC)] vs 54.0 months [95% CI 42.1, NC], respectively; HR 0.67; 95% CI 0.40, 1.14), despite 78% of pts on pbo receiving subsequent osi.

Conclusions

The updated results demonstrate a continued favourable trend for OS benefit with osimertinib. Final OS will be reported when data reach approximately 60% maturity.

Clinical trial identification

NCT03521154; Release date: 11 May 2018.

Editorial acknowledgement

The authors would like to acknowledge Clare McCleverty, PhD, contracted by Ashfield MedComms, an Inizio company, for medical writing support that was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.S. Ramalingam: Financial Interests, Institutional, Funding, Research Funding: Amgen, AstraZeneca, GSK, Pfizer, BMS; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AbbVie. M. Ozguroglu: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals; Financial Interests, Personal, Other, Travel /accommodation support: Regeneron Pharmaceuticals; Financial Interests, Personal, Principal Investigator, Local PI: AstraZeneca, Merck Sharp & Dohme, Pfizer, Bristol Myers Squibb, Gilead, Roche, Astellas, Janssen Pharmaceuticals; Financial Interests, Personal, Member, Steering Committee Member: AstraZeneca, Bayer, Janssen Pharmaceuticals. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, MSD, Merck, Takeda, ONO, Novartis, Lilly, Amgen, Yuhan, Alpha Pharmaceuticals; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, MSD, Merck, Takeda, ONO, Novartis, Lilly, Amgen, Yuhan. J.C. Yang: Financial Interests, Personal, Sponsor/Funding, Research Funding: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roache/Genetech, Takeda, Yuhan Pharmaceuticals, Janssen, Puma Technology, Gilead, GSK, Dizal Pharmaceutica; Financial Interests, Personal, Principal Investigator, Coordinating PI: AstraZeneca, MSD, Dizal Pharmaceutical; Financial Interests, Personal, Member: ASCO, ESMO, IASLC; Financial Interests, Personal, Member, Steering committee member: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Takeda, Yuhan Pharmaceuticals, Janssen, Dizal Pharmaceutical. S. Oizumi: Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo Inc, Pfizer, MSD, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, MSD, Takeda Pharmaceutical. K. Goto: Financial Interests, Personal and Institutional, Sponsor/Funding, Research Funding: AstraZeneca; Financial Interests, Personal, Advisory Role, Speaker, Consultant, Advisor: AstraZeneca. M.A. Cobo Dols: Financial Interests, Personal, Other, Consulting fee: AstraZeneca. T. Hsia: Financial Interests, Personal, Principal Investigator, Local PI: AstraZeneca. F. Fujiki: Non-Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator, Local PI: AstraZeneca; Non-Financial Interests, Personal, Member: ASCO, ESMO; Non-Financial Interests, Personal, Advisory Role, Speaker, Consultant, Advisor: AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Janssen Pharmaceuticals, Daiichi Sankyo. N.I. Valdiviezo Lama: Financial Interests, Personal, Other, Travel support to ELCC 2023: AstraZeneca. T. Kato: Financial Interests, Personal, Advisory Role, Advisory council or committee: AstraZeneca, BeiGene, Chugai, Daiichi Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda; Financial Interests, Personal, Research Grant, Grants or funds: AbbVie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Haihe, Janssen, Merck KGaA, MSD, Novartis, Novocure, Pfizer, Regeneron and Takeda; Financial Interests, Personal, Other, Family member employment: Lilly. X. Huang, A.L. Evans, A.L. Bolanos: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, G Novarti, Yuhan Corporation, Menarini, Mirati Therapeutics Inc, Daiichi Sankyo, Inc., D3 Bio Limited, Simcere; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Hansoh; Non-Financial Interests, Personal, Member of Board of Directors: Innovent BIOLOGICS, INC; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene and Hansoh, Boehringer Ingelheim; Financial Interests, Personal, Other, Speaker, Consultant, Advisor: AstraZeneca, Pfizer, BMS, Hutchison MediPharma, ZaiLab, Yuhan Corporation, Menarini, InventisBio Co. Ltd., Shanghai Fosun Pharmaceutical (Group) Co., Ltd. Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh; Financial Interests, Personal, Other, Steering Committee Member: AstraZeneca, BMS, Yuhan Corporation, Menarini, GSK. All other authors have declared no conflicts of interest.