Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3
Por:
Gray, JE, Markovets, A, Reungwetwattana, T, Majem, M, Nogami, N, Peled, N, Lee, JS, Cho, BC, Chewaskulyong, B, John, T, Han, JY, Sebastian, M, Todd, A, Rukazenkov, Y, Barrett, C, Chmielecki, J, Lee, SM, Ramalingam, SS, Hartmaier, R
Publicada:
1 nov 2024
Ahead of Print:
1 nov 2024
Resumen:
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-na & iuml;ve (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 EGFRTKI 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. (c) 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Filiaciones:
Gray, JE:
H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL USA
Markovets, A:
AstraZeneca, Oncol Data Sci Res & Early Dev, Oncol R&D, Boston, MA USA
Reungwetwattana, T:
Mahidol Univ, Ramathibodi Hosp, Dept Med, Div Med Oncol,Fac Med, Bangkok, Thailand
Majem, M:
Hosp Santa Creu i Sant Pau, Dept Resp Med, Barcelona, Spain
Nogami, N:
Natl Hosp Org, Shikoku Canc Ctr, Dept Thorac Oncol, Minamiumemoto Machi, Matsuyama, Ehime, Japan
Peled, N:
Shaare Zedek Canc Ctr, Sharett Inst Oncol, Dept Radiat Oncol, Jerusalem, Israel
Lee, JS:
Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Div Hematol & Med Oncol, Seoul, South Korea
Cho, BC:
Yonsei Univ, Coll Med, Coll Med, Div Med Oncol, Seoul, South Korea
Chewaskulyong, B:
Chiang Mai Univ, Dept Pathol, Internal Med Oncol Unit, Chiang Mai 50000, Thailand
John, T:
Austin Hlth, Dept Med Oncol, Melbourne, Australia
Han, JY:
Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea
Sebastian, M:
Goethe Univ Frankfurt, Univ Hosp, Dept Med Hematol & Oncol, Frankfurt, Germany
Todd, A:
AstraZeneca, Oncol R&D, Oncol Biometr, Cambridge, England
Rukazenkov, Y:
AstraZeneca, Oncol R&D, Cambridge, England
Barrett, C:
AstraZeneca, Oncol R&D, Translat Med Res & Early Dev, Boston, MA USA
Chmielecki, J:
AstraZeneca, Oncol R&D, Translat Med Res & Early Dev, Boston, MA USA
Lee, SM:
Univ Coll London Hosp, Dept Oncol, Paul OGorman Bldg, London, England
UCL Canc Inst, Paul OGorman Bldg, London, England
Ramalingam, SS:
Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA
Hartmaier, R:
AstraZeneca, Oncol R&D, Translat Med Res & Early Dev, Boston, MA USA
hybrid
|