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

Jhanelle E Gray ¹, Aleksandra Markovets ², Thanyanan Reungwetwattana ³

¹Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
²Oncology Data Science, Research and Early Development, Oncology R&D, AstraZeneca, Boston, Massachusetts, USA.
³Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁴Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁵Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Minamiumemoto-machi, Matsuyama, Japan.
⁶Department of Oncology, The Institute of Oncology, Shaare Zedek Cancer Center & Ben-Gurion University, Jerusalem, Israel.
⁷Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea.
⁸Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁹Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai, Thailand.
¹⁰Department of Medical Oncology, Austin Health, Melbourne, Australia.
¹¹Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea.
¹²Goethe University Frankfurt, University Hospital, Hematology/Medical Oncology, Frankfurt, Germany.
¹³Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
¹⁴Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
¹⁵Translational Medicines, Research and Early Development, Oncology R&D, AstraZeneca, Boston, Massachusetts, USA.
¹⁶Department of Oncology, University College London Hospitals and UCL Cancer Institute, Paul O'Gorman Building, London, United Kingdom.
¹⁷Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.

⁰Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer +

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July 19, 2024

View abstract on PubMed

Summary

Longitudinal circulating tumor DNA (ctDNA) monitoring can detect progressive disease (PD) before radiologic progression in advanced EGFR-mutation-positive non-small cell lung cancer. This approach may offer earlier insights into treatment effectiveness compared to standard imaging methods.

Area Of Science

Oncology
Molecular Diagnostics
Clinical Trials

Background

Circulating tumor DNA (ctDNA) analysis allows for the detection of EGFR tyrosine kinase inhibitor (EGFR-TKI) mutations and resistance mutations in plasma.
Changes in ctDNA levels can dynamically reflect tumor burden and treatment response.
This study investigated the potential of longitudinal ctDNA testing to identify progressive disease (PD) earlier than traditional radiologic assessments.

Purpose Of The Study

To determine if longitudinal EGFR-mutation ctDNA testing could detect progressive disease (PD) before radiologic detection in patients with advanced non-small cell lung cancer (NSCLC).

Main Methods

A retrospective analysis of two Phase 3 clinical trials (FLAURA and AURA3) involving patients with advanced NSCLC and EGFR mutations.
Patients received either osimertinib or comparator EGFR-TKIs (FLAURA) or chemotherapy (AURA3).
ctDNA was monitored longitudinally, and ctDNA PD was compared with RECIST-defined PD and time to first subsequent treatment.

Main Results

ctDNA PD preceded or coincided with RECIST-defined PD in 64% of FLAURA patients and 56% of AURA3 patients.
Median time from ctDNA PD to RECIST PD ranged from 1.5 to 3.4 months across treatment arms and trials.
In the FLAURA trial, ctDNA PD preceded subsequent treatment by a median of 4.7 to 6.0 months.

Conclusions

ctDNA PD was observed to precede or co-occur with radiologically defined PD in approximately 60% of patients with EGFR mutation-positive advanced NSCLC.
Longitudinal ctDNA monitoring shows promise for detecting PD earlier than standard radiologic methods.

Keywords:

Circulating tumor DNA EGFR mutations Non-small cell lung cancer Osimertinib Resistance