Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3
Issued Date
2024-01-01
Resource Type
ISSN
15560864
eISSN
15561380
Scopus ID
2-s2.0-85203015603
Pubmed ID
39029876
Journal Title
Journal of Thoracic Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Thoracic Oncology (2024)
Suggested Citation
Gray J.E., Markovets A., Reungwetwattana T., Majem M., Nogami N., Peled N., Lee J.S., Cho B.C., Chewaskulyong B., John T., Han J.Y., Sebastian M., Todd A., Rukazenkov Y., Barrett C., Chmielecki J., Lee S.M., Ramalingam S.S., Hartmaier R. Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3. Journal of Thoracic Oncology (2024). doi:10.1016/j.jtho.2024.07.008 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101136
Title
Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3
Author's Affiliation
Yonsei Cancer Hospital
Seoul National University Bundang Hospital
National Hospital Organization Shikoku Cancer Center
National Cancer Center, Gyeonggi
Ben-Gurion University of the Negev
University College London Hospitals NHS Foundation Trust
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Hospital de La Santa Creu I Sant Pau
Universitätsklinikum Frankfurt
Austin Health
Moffitt Cancer Center
AstraZeneca
Emory University School of Medicine
Chiang Mai University
Seoul National University Bundang Hospital
National Hospital Organization Shikoku Cancer Center
National Cancer Center, Gyeonggi
Ben-Gurion University of the Negev
University College London Hospitals NHS Foundation Trust
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Hospital de La Santa Creu I Sant Pau
Universitätsklinikum Frankfurt
Austin Health
Moffitt Cancer Center
AstraZeneca
Emory University School of Medicine
Chiang Mai University
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: EGFR tyrosine kinase inhibitor (EGFR-TKI)-sensitizing and -resistance mutations may be detected in plasma through circulating tumor DNA (ctDNA). Circulating tumor DNA level changes reflect alterations in tumor burden and could be a dynamic indicator of treatment effect. This analysis aimed to determine whether longitudinal EGFR-mutation ctDNA testing could detect progressive disease (PD) before radiologic detection. Methods: This was a retrospective, exploratory ctDNA analysis in two phase 3 trials (FLAURA, NCT02296125; AURA3, NCT02151981). Patients had treatment-naïve (FLAURA) or EGFR-TKI pre-treated (AURA3) advanced NSCLC with EGFR mutations and on-study PD (RECIST [Response Evaluation Criteria in Solid Tumors]), with a baseline ctDNA result and EGFR-mutation ctDNA monitoring beyond Cycle 3 Day 1. Patients received osimertinib versus comparator EGFR-TKIs (FLAURA) or chemotherapy (AURA3). Outcomes included time from ctDNA PD to RECIST PD and the first subsequent treatment (FLAURA only). Results: Circulating tumor DNA PD preceded or co-occurred with RECIST-defined PD in 93 out of 146 patients (64%) in FLAURA and 82 out of 146 patients (56%) in AURA3. Median time from ctDNA PD to RECIST-defined PD (mo) was 3.4 and 2.6 in the osimertinib and comparator EGFR-TKI arms (FLAURA) and 2.8 and 1.5 in the osimertinib and chemotherapy arms (AURA3). In FLAURA, the median time from ctDNA PD to the first subsequent treatment (mo) was 6.0 and 4.7 in the osimertinib (n = 51) and comparator EGFR-TKI arms (n = 70). Conclusions: Among patients with EGFR mutation-positive advanced NSCLC receiving EGFR-TKI or chemotherapy with ctDNA data and RECIST-defined PD, ctDNA PD preceded/co-occurred with RECIST-defined PD in approximately 60% of cases. Longitudinal ctDNA monitoring may detect PD before radiologic PD.