Clinical Utility of Combined Plasma and Tissue NGS in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer

Introduction: The incremental clinical value of performing both tissue and plasma next-generation sequencing (NGS) to detect actionable alterations (AA) at diagnosis in patients with advanced non-small cell lung cancer (aNSCLC) has not been comprehensively assessed. Methods: We conducted a study with two aNSCLC cohorts, prospectively assessed with tissue and plasma NGS at diagnosis. Guardant360 CDx and FoundationOne Liquid CDx were used in cohort 1 (N=127) and cohort 2 (N=149), respectively. We considered AA according to ESCAT I-III levels. Undetectable ctDNA and unavailable tissue were considered non-informative results. Results: AA were found in 50/127 (39%) and 65/149 (44%) patients in cohorts 1 and 2, respectively (Figure 1). In cohort 1, AA were detected only in plasma in 14/50 (28%) and only in tissue in 9/50 (18%). In the 14 cases with AA only detected in plasma, 3 had informative tissue results (1 EGFR and 1 KRAS G12C mutations detected in plasma but not in tissue). In the 9 cases with AA only detected in tissue, 6 had informative plasma results (1 ALK fusion, 1 ERBB2 amplification, 1 EGFR and 2 KRAS G12C mutations detected in tissue but not in plasma). In cohort 2, AA were detected only in plasma in 22/65 (34%) and only in tissue in 15/65 (23%). In the 22 cases with AA only detected in plasma, 11 had informative tissue results (1 RET and 1 ALK fusions, 3 ERBB2 alterations, 2 KRAS G12C mutations detected in plasma but not in tissue). In the 15 cases with AA only detected in tissue, 6 had informative plasma results (3 EGFR mutations, 1 ROS1 fusion and 2 ERBB2 amplifications detected in tissue but not in plasma). Conclusion: Due to data observed, plasma NGS should be considered when AA are not detected by tissue, and vice versa, in patients with newly diagnosed aNSCLC.