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Clinical Trial
. 2025 May;20(5):641-650.
doi: 10.1016/j.jtho.2024.12.023. Epub 2024 Dec 26.

Neoadjuvant and Adjuvant Osimertinib in Stage IA to IIIA, EGFR-Mutant NSCLC (NORA)

Jii Bum Lee  1 , Su-Jin Choi  1 , Hyo Sup Shim  2 , Byung Jo Park  3 , Chang Young Lee  3 , Sumedha Sudhaman  4 , Sharlene Velichko  4 , Min Hee Hong  1 , Byoung Chul Cho  1 , Sun Min Lim  5
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Free article
Clinical Trial

Neoadjuvant and Adjuvant Osimertinib in Stage IA to IIIA, EGFR-Mutant NSCLC (NORA)

Jii Bum Lee et al. J Thorac Oncol. 2025 May.
Free article

Abstract

Introduction: Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB to IIIA NSCLC harboring EGFR mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).

Methods: This is a single-center, pilot study of patients with clinical stage IA to IIIA NSCLC (American Joint Committee on Cancer eighth edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838). Patients were treated with two 28-day cycles of neoadjuvant osimertinib followed by surgical resection and three years of adjuvant osimertinib. The primary endpoint was the objective response rate after two cycles of neoadjuvant treatment. Secondary endpoints included the pathologic complete response rate and major pathologic response rate. Exploratory objectives included the correlation of longitudinal circulating tumor DNA testing (Signatera) and response to neoadjuvant osimertinib.

Results: A total of 25 patients were enrolled and treated with neoadjuvant osimertinib, and all patients received surgical resection with R0 resection. The objective response rate was 44% (n = 11) all of which were partial responses. Fourteen patients (56%) reported stable disease after neoadjuvant osimertinib. The major pathologic response and pathologic complete response rates were 24% (n = 6) and 0%, respectively. None of the patients received adjuvant chemotherapy. The median disease-free survival was not reached at a median follow-up of 31 months (range: 13.8-38.6 mo). Six patients (30%) were circulating tumor DNA-positive at baseline and achieved clearance after 1 cycle of neoadjuvant osimertinib. There were no grade 3 adverse events during neoadjuvant treatment.

Conclusions: Two cycles of neoadjuvant osimertinib did not meet its primary endpoint of ORR. Neoadjuvant osimertinib is a feasible approach with a manageable safety profile in resectable EGFR-mutant NSCLC.

Keywords: Adjuvant; Neoadjuvant; Non-small cell lung cancer; Osimertinib; Stage IA-IIIA.

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Conflict of interest statement

Disclosure Dr. Lee reports research grants from Yuhan. Dr. Sudhaman and Dr. Velichko are full-time employees at Natera, Inc. with stock or options to own stock. Dr. Hong reports grants from AstraZeneca, Merck Sharp & Dohme, Novartis, and Yuhan; personal fees from AstraZeneca, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Ono Pharmaceutical, Takeda, Roche, Pfizer, and Yuhan; and participating in clinical trials funded by AbbVie, IMPACT, Ignyta, Loxo Oncology, Novartis, Merck Sereno, ORIC, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, Pfizer, and Yuhan outside the submitted work. Dr. Cho reports the following: Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Advisory board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc. (Financial interests); Member of the board of directors: Interpark Bio Convergence Corp., J INTS BIO (Financial interests); Stocks/shares: TheraCanVac Inc, Gencurix Inc, Bridgebiotherapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO (Financial interests); Royalties: Champions Oncology (Financial interests); Research grants: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi (Financial interests); Advisory role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi (Financial interests); Other: DAAN Biotherapeutics (Founder). Dr. Lim reports grants from Yuhan, Beigene, Boehringer Ingelheim, BridgeBio Therapeutics, Roche, GSK, Jiangsu Hengrui, AstraZeneca, Lily, Takeda, Daiichi Sankyo and J Ints Bio. The remaining authors declare no conflict of interest.

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