Smadar Laufer-Geva1, Anna Belilovski Rozenblum1, Tal Twito2, Roxana Grinberg3, Addie Dvir2, Lior Soussan-Gutman2, Maya Ilouze4, Laila C Roisman3, Elizabeth Dudnik4, Alona Zer4, Ofer Rotem4, Richard B Lanman5, Nir Peled6. 1. Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 2. Teva Pharmaceutical Industries, Ltd., West Chester, Pennsylvania. 3. The Legacy Heritage Oncology Center and Dr. Larry Norton Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel. 4. Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel. 5. Guardant Health, Inc., Redwood City, California. 6. The Legacy Heritage Oncology Center and Dr. Larry Norton Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel. Electronic address: nirp@clalit.org.il.
Abstract
INTRODUCTION: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLC patients. Although plasma-detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions. METHODS: This retrospective study of stage IIIB/IV NSCLC patients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable GAs. RESULTS: We consecutively tested 116 NSCLC patients, 41.4% before first-line therapy (group A), 34.5% upon progression on chemotherapy or immunotherapy (group B1), and 24.1% upon progression on EGFR tyrosine kinase inhibitors (group B2). Targetable GAs were found in 31% of group A (15 of 48 patients), 32.5% in group B1 (13 of 40 patients) and 71% in group B2 (20 of 28 patients). Treatment decision was changed to targeted therapy in 23% (11 of 48 patients), 25% (10 of 40 patients) and 32% (9 of 28 patients), respectively (total cohort 26%; 30/116). Objective response rate (Response Evaluation Criteria in Solid Tumors) was 43% (12 of 28 patients) including one complete response, partial response in 39% (11 of 28 patients), stable disease in 32% (9 of 28 patients), and progressive disease in 25% (7 of 28 patients). Disease control rate was 75% for 5 months median treatment duration. CONCLUSIONS: Comprehensive cfDNA testing impacted clinical decisions in one-quarter to one-third of initial and subsequent lines of treatment in advanced NSCLC patients. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.
INTRODUCTION: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLCpatients. Although plasma-detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions. METHODS: This retrospective study of stage IIIB/IV NSCLCpatients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable GAs. RESULTS: We consecutively tested 116 NSCLCpatients, 41.4% before first-line therapy (group A), 34.5% upon progression on chemotherapy or immunotherapy (group B1), and 24.1% upon progression on EGFR tyrosine kinase inhibitors (group B2). Targetable GAs were found in 31% of group A (15 of 48 patients), 32.5% in group B1 (13 of 40 patients) and 71% in group B2 (20 of 28 patients). Treatment decision was changed to targeted therapy in 23% (11 of 48 patients), 25% (10 of 40 patients) and 32% (9 of 28 patients), respectively (total cohort 26%; 30/116). Objective response rate (Response Evaluation Criteria in Solid Tumors) was 43% (12 of 28 patients) including one complete response, partial response in 39% (11 of 28 patients), stable disease in 32% (9 of 28 patients), and progressive disease in 25% (7 of 28 patients). Disease control rate was 75% for 5 months median treatment duration. CONCLUSIONS: Comprehensive cfDNA testing impacted clinical decisions in one-quarter to one-third of initial and subsequent lines of treatment in advanced NSCLCpatients. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.
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