Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer

Osimertinib-a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor-is recommended as adjuvant therapy for resected stage IB-IIIA epidermal growth factor receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall survival improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of 3 years adjuvant treatment in ADAURA suggests that some patients may benefit from longer adjuvant osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence in an exploratory post hoc analysis of 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA. MRD preceded imaging DFS events in this study by a median of 4.7 (95% confidence interval, 2.2-5.6) months. DFS and MRD event-free rate at 36 months was 86% versus 36% for patients in the osimertinib versus placebo groups (hazard ratio, 0.23 (95% confidence interval, 0.15-0.36)). In the osimertinib group, DFS or MRD events were detected in 28 (25%) patients; most events occurred following osimertinib cessation (19 of 28, 68%) and within 12 months of stopping osimertinib (11 of 19, 58%). At 24 months after osimertinib, the DFS and MRD event-free rate was 66%. In this study, MRD preceded DFS events in most patients across both arms. DFS and MRD event-free status was maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up, with most MRD or DFS events occurring after osimertinib treatment discontinuation or completion. MRD detection could potentially identify patients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 .

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Publication Details

Journal
Nature Medicine
Published
2025-03-17
DOI
https://doi.org/10.1038/s41591-025-03577-y
Citations
33
Primary Topic
Lung Cancer Treatments and Mutations
Type
article
Field-Weighted Citation Impact
50.11

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article

Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer

Roy S. Herbst, Yuri Rukazenkov, Mustafa Özgüroğlu, Myung‐Ju Ahn et al.
33 citations
Nature Medicine
Lung Cancer Treatments and Mutations
50.11
article

Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer

Roy S. Herbst, Yuri Rukazenkov, Mustafa Özgüroğlu, Myung‐Ju Ahn, Jonathan Wade Goldman, M. Pérol, Masahiro Tsuboi, Ryan J. Hartmaier, Aleksandra Markovets, Margarita Majem, Laura Bonanno, Dariusz M. Kowalski, Preetida J. Bhetariya, Marcello Tiseo, К. К. Лактионов, Jacqulyne Robichaux, Manuel Dómine, Thomas John, Terufumi Kato, Yi-Long Lung Cancer Wu, Virote Sriuranpong, Caitlin Muldoon, Christian Grohé
article en
33 citations

Abstract

Osimertinib-a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor-is recommended as adjuvant therapy for resected stage IB-IIIA epidermal growth factor receptor-mutated non-small-cell lung cancer, based on significant disease-free survival (DFS) and overall survival improvement shown in the previously reported phase 3 ADAURA trial. A trend toward an increased DFS event rate after completion of 3 years adjuvant treatment in ADAURA suggests that some patients may benefit from longer adjuvant osimertinib treatment. We therefore explored whether tumor-informed, circulating tumor DNA-based, molecular residual disease (MRD) could predict recurrence in an exploratory post hoc analysis of 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA. MRD preceded imaging DFS events in this study by a median of 4.7 (95% confidence interval, 2.2-5.6) months. DFS and MRD event-free rate at 36 months was 86% versus 36% for patients in the osimertinib versus placebo groups (hazard ratio, 0.23 (95% confidence interval, 0.15-0.36)). In the osimertinib group, DFS or MRD events were detected in 28 (25%) patients; most events occurred following osimertinib cessation (19 of 28, 68%) and within 12 months of stopping osimertinib (11 of 19, 58%). At 24 months after osimertinib, the DFS and MRD event-free rate was 66%. In this study, MRD preceded DFS events in most patients across both arms. DFS and MRD event-free status was maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up, with most MRD or DFS events occurring after osimertinib treatment discontinuation or completion. MRD detection could potentially identify patients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 .

Nature MedicineVol. 31(6)
AstraZeneca (United Kingdom) (GB), University of Parma (IT), University of Padua (IT), Chulalongkorn University (TH), University of California, Los Angeles (US), Peter MacCallum Cancer Centre (AU), Hospital de Sant Pau (ES), Samsung Medical Center (KR), King Chulalongkorn Memorial Hospital (TH), Yale Cancer Center (US), Kanagawa Prefectural Hospital Organization (JP), Istituto Oncologico Veneto (IT), Istanbul University-Cerrahpaşa (TR), Ministry of Health of the Russian Federation (RU), Centre de Recherche en Cancérologie de Lyon (FR), Hospital Universitario Fundación Jiménez Díaz (ES), National Cancer Center Hospital East (JP), Guangdong Academy of Medical Sciences (CN), AstraZeneca (United States) (US), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Evangelische Lungenklinik Berlin (DE), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Guangdong Provincial People's Hospital (CN), Kanagawa Cancer Center, Southern Medical University (CN), Sungkyunkwan University (KR)
AstraZeneca
Openalex Percentile: Top 0%
Lung Cancer Treatments and Mutations
50.11
DOIOpen Access PDFOpenAlex
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