Abstract 5394: The clinical impact of multiplex ctDNA gene analysis in lung cancer
Authors: Geva Smadar , Rozenblum Anna Belilovski , Twito Tal , Dvir Addie , Soussan-Gutman Lior , Ilouze Maya , Roisman Laila C. , Dudnik Elizabeth , Zer Alona , Lanman Richard B. , Peled Nir 
Published: July 2017

Abstract
Background: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. Currently there is insufficient data in regard to the impact of ctDNA analysis on clinical decision making. In this study, we evaluated the clinical utility of ctDNA sequencing on treatment strategy and progression-free survival.
Methods: In this retrospective study, data was collected from files of 92 NSCLC patients monitored between the years 2014-2016 at the Thoracic Center Unit at Davidoff Cancer Center, Rabin Medical Center, Israel. Plasma samples from stage IIIb/IV non-small cell lung cancer (NSCLC) patients were analyzed by a commercial test (Guardant 360), using hybrid capture, single molecule barcoding and massively parallel paired-end synthesis to sequence a targeted gene panel. This test allows the detection of somatic alterations such as point mutations, indels, fusions and copy number amplifications.
Results: 92 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, male:female ratio was 1:1.6. 40% (37/92) were never-smokers, 84% (77/92) had adenocarcinoma. 38% (35/92) performed ctDNA analysis before 1st line therapy and 62% (57/92) on progression. ctDNA analysis yielded lung cancer related actionable mutations in total 39% (36/92) of the patients; 31% (11/35) among upfront testing and 44% (25/57) among patients at progression on matched therapy. Treatment decision was taken toward targeted therapy subsequent to NGS analysis in 23% (8/35) and 26% (15/57) respectively (total 25%; 23/92). 53 individual actionable genomic alterations were found. The most common genes were sensitizing EGFR mutations (47.2%; 25/53), MET amplifications and/or exon 14 skipping mutations (17%; 9/53) and resistance EGFR mutations (13.2%; 7/53). Response assessment (RECIST) for 18 patients with evaluable response to targeted therapy showed complete response in 6% (1/18), partial response in 39% (7/18), stable disease in 22% (4/18) and progressive disease in 33% (6/18). Total objective response rate (ORR) was 45% and disease control rate was 67%.
Conclusions: Comprehensive ctDNA testing revealed possible treatment options for two-thirds of patients analyzed. ctDNA analysis impacted clinical decision making in a quarter of the patients. Although this topic needs to be further assessed in large randomized controlled trials, these positive results emphasize the utility of liquid biopsy analysis to guide clinicians to select the right therapy for the right patient.
Citation Format: Smadar Geva, Anna Belilovski Rozenblum, Tal Twito, Addie Dvir, Lior Soussan-Gutman, Maya Ilouze, Laila C. Roisman, Elizabeth Dudnik, Alona Zer, Richard B. Lanman, Nir Peled. The clinical impact of multiplex ctDNA gene analysis in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5394. doi:10.1158/1538-7445.AM2017-5394