Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3

作者：Jhanelle E. Gray, Aleksandra A. Markovets, Thanyanan Reungwetwattana, Margarita Majem, Naoyuki Nogami, Nir Peled, Jong Seok Lee, Byoung Chul Cho, Busayamas Chewaskulyong, Tom John, Ji‐Youn Han, Martin Sebastian, Alexander Robertus Todd, Yuri Rukazenkov, Carl J. Barrett, Juliann Chmielecki, Siow Ming Lee, Suresh S. Ramalingam, Ryan James Hartmaier · 发表于：Journal of Thoracic Oncology · 年份：2024 · DOI：10.1016/j.jtho.2024.07.008 · 被引用次数：28 · 研究领域：Cancer Genomics and Diagnostics、Lung Cancer Treatments and Mutations、Colorectal Cancer Treatments and Studies

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) an...