Combining plasma and tissue next-generation sequencing provides optimal treatment selection for metastatic NSCLC: A comparative study.

Abstract

e21193 Background: 64% of all NSCLC patients in the USA with targetable mutations do not receive therapy due to clinical practice gaps around biomarker identification, including guideline-recommended alterations. Similar diagnostic and access challenges are also seen in Asia, but the scope of these challenges may differ due to the different mutation profiles of NSCLC. To determine the biomarker gaps involved, we conducted a study evaluating 38 metastatic NSCLC patients who received 3 diagnostic molecular workflows, and compared all 3 results to determine potential practice gaps. This is the first study to our knowledge that evaluates 3 different diagnostic workflows for one cohort to determine relative performance. Methods: 386 newly diagnosed and pathologically confirmed patients with metastatic lung cancer were managed at our hospital over Aug 21 - Sep 22. 38 metastatic non-squamous NSCLC patients were recruited prospectively. The patients received 1 plasma NGS tests (LiquidHALLMARK, Lucence, Singapore), 1 tissue comprehensive genomic profiling (CGP) test, and a panel of single-gene molecular tests (Idylla EGFR, ALK-IHC, ROS1-FISH, PD-L1 IHC). Results: Of the 38 patients recruited for the prospective trial, liquid biopsy identified 24 actionable alterations (TAT 3-13 days), tissue NGS identified 23 actionable alterations (TAT 11-27 days) and single gene testing approach provided 17 actionable alterations (TAT variable). 6 patients did not have available tissue reports. In terms of patient numbers, liquid biopsy detected at least one G9 biomarker in 21/38 patients and tissue NGS detected at least one G9 biomarker in 22/32 patients. Combining tissue NGS and liquid biopsy provided 26/38 (68.4%) patients with targeted treatment options. Single gene testing identified at least one G9 biomarker in 16/38 (42.1%) patients. Combining tissue NGS, liquid biopsy and single gene test improved sensitivity to 73.7% (28/38 patients). Overall, an estimated 1 in 4 NSCLC patients (26.4%) would have been identified with a diagnostic strategy using combined tissue and liquid NGS, over current conventional single gene testing approaches. Conclusions: Combining tissue and liquid NGS profiling provides the best treatment selection outcomes for patients with metastatic NSCLC. Our study highlighted that a quarter of NSCLC patients in Singapore would be identified for eligible targeted treatments from adopting a nationwide NGS testing approach, ideally tissue and liquid combined, to improve cancer services.