Longitudinal Analyses of Circulating-Tumor DNA for Detection of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Progression During Treatment: Data From FLAURA and AURA3.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-sensitizing and -resistance mutations may be detected in plasma via circulating tumor DNA (ctDNA). ctDNA 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. 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 non-small cell lung cancer (NSCLC) with EGFR mutations and on-study PD (RECIST), 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 to first subsequent treatment (FST; FLAURA only). ctDNA PD preceded/co-occurred with RECIST-defined PD in 93/146 (64%) patients in FLAURA and 82/146 (56%) in AURA3. Median time from ctDNA PD to RECIST-defined PD (months) 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, median time from ctDNA PD to FST (months) was 6.0 and 4.7 in the osimertinib (n = 51) and comparator EGFR-TKI arms (n = 70). 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.

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