Abstract 616P
Background
Osimertinib (osi) is a CNS-active, 3rd-generation EGFR-tyrosine kinase inhibitor (TKI) recommended for EGFRm advanced NSCLC and as adjuvant treatment (tx) for resected EGFRm NSCLC. In the global, double-blind, placebo (PBO)-controlled Phase III LAURA study (NCT03521154), osi demonstrated statistically significant improvements in progression-free survival (PFS) in pts with UR stage III EGFRm NSCLC without progression after definitive CRT (hazard ratio [HR], 0.16; 95% CI 0.10, 0.24; p<0.001). Here we report post-progression outcomes.
Methods
Pts were randomised 2:1 to osi 80 mg or PBO QD until progression assessed by blinded independent central review (BICR) or discontinuation. Osi was offered after progression for both arms. Primary endpoint: PFS by BICR, per RECIST 1.1; secondary endpoints included time to first subsequent therapy (TFST), second PFS (PFS2), and time to second subsequent therapy (TSST).
Results
At DCO (5 Jan 2024), 63 / 143 (44%) and 66 / 73 (90%) randomised pts discontinued osi and PBO, respectively. Median time to tx discontinuation or death was longer with osi vs PBO; 40.3 (95% CI 32.7, not calculable [NC]) vs 8.3 (95% CI 6.1, 11.1) months (mo), HR 0.21 (95% CI 0.14, 0.32). Of pts who discontinued tx, 28 (44%) in the osi arm and 57 (86%) in the PBO arm received a subsequent EGFR-TKI; 14 (22%) and 50 (76%) pts, respectively, received osi as first subsequent tx. More pts in the osi arm received radiotherapy as first subsequent tx vs PBO (17 [27%] vs 5 [8%], respectively). Improvements in median TFST, PFS2 and TSST were observed with osi vs PBO; TFST: 43.8 (95% CI 38.9, NC) vs 9.5 (95% CI 6.6, 11.5) mo, HR 0.13 (95% CI 0.08, 0.21); PFS2: 48.2 (95% CI, 44.4, NC) vs 47.4 (95% CI 28.2, NC) mo, HR 0.62 (95% CI 0.35, 1.08); TSST: not reached (95% CI 44.4, NC) vs 47.4 mo (95% CI 34.1, NC), HR 0.51 (95% CI 0.28, 0.91).
Conclusions
Clinically meaningful improvements in TFST, PFS2 and TSST with osi vs PBO indicated that PFS benefit was preserved after first progression through subsequent lines of tx, despite high cross-over in the PBO arm. These data support the long-term benefits of osi for pts with UR stage III EGFRm NSCLC.
Clinical trial identification
NCT03521154; 11 May 2018.
Editorial acknowledgement
Medical writing assistance was provided by Yasmin Issop, PhD, of Ashfield MedComms, an Inizio Company.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Ozguroglu: Financial Interests, Personal, Advisory Board: MSD, Regeneron; Other, Personal, Invited Speaker: Regeneron; Financial Interests, Personal, Local PI: AstraZeneca, MSD, Pfizer, BMS, Gilead, Roche, Astellas, Janssen; Financial Interests, Personal, Steering Committee Member: AstraZeneca, Bayer, Janssen. 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, 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, Coordinating PI: AstraZeneca, MSD, Dizal Pharmaceutical; Financial Interests, Personal, Member: ASCO, ESMO, IASLC; Financial Interests, Personal, Research Funding: AstraZeneca, Roche; Financial Interests, Personal, 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, Research Funding: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. M. Cobo Dols: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. T. Hsia: Financial Interests, Personal, Local PI: AstraZeneca. F.K. Fujiki: Non-Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Local PI: AstraZeneca; Non-Financial Interests, Personal, Membership or affiliation: ASCO, ESMO; Non-Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, MSD, BMS, Janssen, Daiichi Sankyo. L. Poole: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca, Lilly, Takeda. A.L. Evans: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. E. Armenteros Monterroso: Financial Interests, Personal, Full or part-time Employment: 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; Financial Interests, Personal, Member of Board of Directors: Independent director of Board member of Innovent BIOLOGICS, INC; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Beigene and Hansoh, Boehringer Ingelheim; Financial Interests, Personal, 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, Steering Committee Member: AstraZeneca, BMS, Yuhan Corporation, Menarini, GSK. All other authors have declared no conflicts of interest.