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, 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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