Evaluation of liquid biopsies for molecular profiling in untreated patients with stage III/IV non-small cell lung cancer (NSCLC).

Abstract

11540 Background: Molecular profiling is limited by tumour heterogeneity and access to sufficient tissue for comprehensive analysis. Circulating tumour DNA (ctDNA) can be used as a minimally-invasive liquid biopsy for mutation detection, quantification and monitoring for personalised treatment strategies. Methods: We recruited 110 patients into a prospectively-designed study for Stage III/IV NSCLC patients intended to initiate 1stline platinum-based chemotherapy. Blood collections (10ml K2-EDTA) were performed prior to treatment and analysed by InVision (enhanced tagged-amplicon sequencing) using a 34-gene panel. Tissue biopsies, when available, were analysed by NGS (Ion-Torrent, Sanger) for concordance analysis. To evaluate correlation with outcome, repeat blood collections were performed in selected patients. Results: 110 NSCLC pts were included (61% male, 14% never-smoker, and 70% adenocarcinoma). ctDNA profiling detected mutations in 83 pts (79%). TP53 (44%), KRAS (17%), STK11 (18%; 11/19 with KRAS/STK11) and EGFR (10%) were the commonest abnormalities detected. Additionally, MET (6%), ERBB2 (6%), PIKC3A (6%) and BRAF (4%) mutations and EGFR, MET, ERBB2 amplifications were detected in 2% of patients, respectively. 20% of the mutations detected in ctDNA were observed at < 0.5% allele fraction, with 6% between 0.03%-0.25% AF. Tissue was available in 44 pts; somatic mutations were detected in 73%. Tissue & liquid concordance was 92.3%. 10 pts (23%) reported as tissue negative had a positive liquid biopsy. 33 advanced NSCLC patients were evaluated for longitudinal serial ctDNA monitoring up to cycle 4 of chemotherapy; the ratio of mutated molecules between D1 and D42 was significantly correlated with change in RECIST 1.1 measurement at D42 (p-value = 0.002625 CI 95% 0.298, 0.875). Conclusions: ctDNA can be used as a ‘liquid biopsy’ for molecular profiling of NSCLC patients to detect clinically relevant and actionable mutations when tissue biopsy is unavailable. Liquid biopsies can be used longitudinally and may provide an early surrogate for response evaluation by radiographic RECIST.