933MO Longitudinal monitoring of circulating tumor DNA from plasma in patients with curative resected stage IA-IIIA EGFR mutant non-small cell lung cancer

Abstract

For patients with early stage epidermal growth factor receptor mutation positive (EGFR-M+) non-small cell lung cancer (NSCLC), curative surgery followed by adjuvant chemotherapy is considered the standard of care. Recently, based on the ADAURA study, osimertinib was approved in resected stage IB-IIIA EGFR-M+ NSCLC. The circulating tumor DNA (ctDNA) provides a potential biomarker for detection of minimal residual disease (MRD) and recurrence. We investigated the longitudinal monitoring of ctDNA test in early stage EGFR-M+ NSCLC. Between August 2015 and October 2017, 278 patients with curative resected, stage IA-IIIA EGFR-M+ NSCLC were enrolled. Radiological follow-up was accompanied with longitudinal monitoring of ctDNA using a droplet digital PCR from baseline and follow-up per protocol until 5 years or recurrence. Median follow-up duration was 62.0 months (range, 1.5-774). Among 278 patients, stage IA, IB, IIA, IIB, and IIIA comprised 60.1%, 18.3%, 10.1%, 2.2%, and 9.4%, respectively. The EGFR exon 19 del was 60.1% and L858R was 39.9%. The 3-year DFS rate for each stage was 95%, 78%, 58%, 50%, and 32%, respectively. Among 278 patients, baseline ctDNA was detected in 67 (24.1%) patients: 23.4% (stage IA), 17.6% (IB), 17.9% (IIA), 50.0% (IIB), and 42.3% (IIIA) (P=0.06). In 76.1% (51 of 67) of patients with baseline ctDNA, it was cleared up 4 weeks after surgery. Patients were classified into three groups according to the positivity of ctDNA (Group A: baseline ctDNA negative (n=211), Group B: baseline ctDNA positive, but MRD negative (n=51), Group C: baseline ctDNA positive, but MRD positive (n=16)). The 3-year DFS rate was significantly different among the three groups (83.3% for Group A, 78% for Group B, and 50% for Group C, respectively, P=0.02). After adjusting for clinicopathologic variables, ctDNA group (HR 1.27, 95% CI 1.03-1.57, P=0.03) still remains an independent risk factor regardless stage for DFS. These results suggest that patients with baseline ctDNA positive or MRD positive were associated with poor DFS in curative resected stage IA-IIIA EGFR M+ NSCLC. Further detailed results of longitudinal monitoring of ctDNA and clinical recurrence will be presented.