The Clinical Impact of Comprehensive cfDNA Genomic Testing in Lung Cancer

Background: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables a noninvasive option for comprehensive genomic analysis of lung cancer patients. Currently there is insufficient data in regard to the impact of cfDNA analysis on clinical decision making. In this study, we evaluated the clinical utility of cfDNA sequencing on treatment strategy and progression-free survival in non-small cell lung cancer (NSCLC) patients. Methods: In this retrospective study, data was collected from files of 116 NSCLC patients monitored between the years 2014–2017 in Israel. Plasma samples from stage IIIb/IV 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: 116 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, male: female ratio was 1:1.7. 40% (47/116) were never-smokers, 83% (96/116) had adenocarcinoma. 41.4% (48/116) were tested before 1st line therapy (Group A), 34.5% (40/116) upon progression on chemotherapy or immunotherapy (Group B1) and 24.1% (28/116) upon progression on EGFR TKIs (Group B2). The most common genes were EGFR sensitizing mutations (25.9%, 30/116), MET amplifications and/or exon 14 skipping mutations or resistance point mutation (9.5%, 11/116) and EGFR T790M mutations (6.9%, 8/116). Clinical outcome of cfDNA analysis and targeted therapy for the entire cohort and for each group are summarized in the Table.Table(Abstract 146P) Clinical Outcome of cfDNA Analysis and Targeted TherapyTotal (n = 116)Group A (n = 48)Group B1 (n = 40)Group B2 (n = 28)Drug-associated actionable Mutations (On/Off Lable)65% (75/116)65% (31/48)52.5% (21/40)82% (23/28)Lung Cancer Related Actionable Mutations (NCCN guidelines)41% (48/116)31% (15/48)32.5% (13/40)71% (20/28)Tretmanet change (Impact on Decision)26% (30/116)23% (11/48)25% (10/40)32% (9/28)Response Evaluable93% (28/30)82% (9/11)100% (10/10)100% (9/9)Response not Evaluable7% (2/30)18% (2/11) Early cessation of treatment d/t toxicity0% (0/10)0% (0/9)Response Assessment (RECIST): CR4% (1/28)0% (0/9)0% (0/10)11% (1/9)Response Assessment (RECIST): PR39% (11/28)44% (4/9)30% (3/10)44% (4/9)Response Assessment (RECIST): SD32% (9/28)56% (5/9)20% (2/10)22% (2/9)Response Assessment (RECIST): PD25% (7/28)0% (0/9)50% (5/10)22% (2/9)Objective Response Rate43% (12/28)44% (4/9)30% (3/10)55.5% (5/9)Disease Control Rate75% (21/28)100% (9/9)50% (5/10)78% (7/9)Median Duration of Treatment5 months (6/28 ongoing)9 months (4/9 ongoing)3.5 months (0/10 ongoing)4 months (2/9 ongoing)Durable Disease Control Rate (over 4 months)43% (13/30)64% (7/11)20% (2/10)44% (4/9)Median PFS3.6 months7.3 months2.5 months3.3 months Open table in a new tab Conclusions: This study extends the evidence for clinical utility of comprehensive NGS testing by demonstrating durability of response to plasma-detected genomic alterations. cfDNA NGS changes treatment decisions in a significant number of patients in this retrospective study. It also has the potential to reduce undergenotyping of advanced NSCLC patients, while reducing costs and complications of biopsies, and facilitating more precise use of targeted therapy as well as immunotherapy. Legal entity responsible for the study: Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel. Funding: Has not received any funding Disclosure: S. Geva: Travel grant from Teva Pharmaceuticals, Honorarium from Guardant Health. A. Dvir, L. Soussan-Gutman: Employee of Oncotest (subsidiary of Teva pharmaceuticals), the distributor of Guardant360 in Israel. L.C. Roisman: Lectures fees: Roche, MSD, Pfizer, Astrazenca. A. Zer: Personal fees from Roche, grants and personal fees from BMS, personal fees from AstraZeneca, personal fees from BI, outside the submitted work. N. Peled: Advisor & Honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.