Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment : Data From FLAURA and AURA3
Gray, Jhanelle E. (H. Lee Moffitt Cancer Center & Research Institute)
Markovets, Aleksandra (AstraZeneca)
Reungwetwattana, Thanyanan (Mahidol University)
Majem Tarruella, Margarita (Institut de Recerca Sant Pau)
Nogami, Naoyuki (National Hospital Organization Shikoku Cancer Center)
Peled, Nir (Shaare Zedek Cancer Center & Ben-Gurion University)
Lee, Jong-Seok (Seoul National University Bundang Hospital)
Cho, Byoung Chul (Yonsei University College of Medicine)
Chewaskulyong, Busayamas (Chiang Mai University)
John, Thomas (Austin Health)
Han, Ji-Youn (Center for Lung Cancer. National Cancer Center)
Sebastian, Martin (Goethe University Frankfurt)
Todd, Alexander (AstraZeneca. Oncology R&D)
Rukazenkov, Yuri (AstraZeneca Oncology R&D)
Barrett, Carl (Translational Medicines. Research and Early Development. Oncology R&D. AstraZeneca)
Chmielecki, Juliann (Translational Medicines. Research and Early Development. Oncology R&D. AstraZeneca)
Lee, Siow Ming (University College London Hospitals and UCL Cancer Institute. Paul O'Gorman Building)
Ramalingam, Suresh S. (Emory University School of Medicine)
Hartmaier, Ryan (Translational Medicines. Research and Early Development. Oncology R&D. AstraZeneca)
Universitat Autònoma de Barcelona

Date:	2024
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Circulating tumor DNA ; EGFR mutations ; Non-small cell lung cancer ; Osimertinib ; Resistance
Published in:	Journal of thoracic oncology, Vol. 19 Núm. 11 (november 2024) , p. 1525-1538, ISSN 1556-1380

DOI: 10.1016/j.jtho.2024.07.008
PMID: 39029876

14 p, 530.8 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
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