Effect of plasma-based molecular testing in patients with newly diagnosed advanced NSCLC on initiation of targeted agents in patients with targetable genomic alterations: A real world experience from the Middle East.
Authors: Anjana Joel, Zamzam Al-Hashami, Shafquat Ali Khan, Prashant Ajit Deshpande, Ramesh Babu Telugu, Abdallah Bilal Khreis, Jayakrishnan Nair, Sami M. Bennji
Journal: Journal of Clinical Oncology (2024)

e20514 Background: The treatment of metastatic non-small cell lung cancer ( m-NSCLC) is personalized and driven by mutational profiling of the tumour tissue at diagnosis. This study evaluates the additional clinical utility of plasma based molecular testing towards shortening time to initiation of treatment and detection of targetable mutations in a cohort of patients with newly diagnosed m-NSCLC. Methods: This is a retrospective analysis of patients with newly diagnosed advanced NSCLC referred to the Thoracic Oncology Program between September 2021 to December 2023, who underwent “paired” plasma based circulating tumour ( ct-DNA ) and tissue based next generation sequencing (NGS) testing (done less than 4 weeks apart). ct-DNA testing was performed using the Oncomine Pancancer NGS Assay (Thermo Scientific) that screens for single nucleotide variants (SNV) in hotspot regions of 52 and common fusions involving 12 genes respectively. Tissue NGS testing was performed using Oncomine Comprehensive Assay Plus (Thermo Scientific); a panel covering ~500 genes capable of identifying all single nucleotide variants, indels, fusions and copy number variants (CNV). Patient demographics and clinicopathological characteristics were collected by retrospective review of electronic medical records (EMR). Results: Among 36 patients, the median age was 66.0 years (range: 32-66), 25 (69.4%) were males, and 16 (44.4%) were never smokers. Thirty (83.3%) had adenocarcinoma and 33 (91.67%) had stage IV NSCLC. The mutation detection rate of ct-DNA was 66.7% with a concordance of 58.3% between ct-DNA and tissue NGS testing. The median turnaround time (TAT) from sample collection to reporting were12 days (IQR:8-15) and 14 days (IQR:9-24.50) for ct-DNA and tissue NGS testing respectively. Among 31 patients who started treatment, the median time to initiation of 1 st line treatment was 26 days from date of first visit (IQR:18-42). Fifteen(41.7%), 6(16.7%) and 10(27.8%) started first line targeted therapy, chemotherapy and chemoimmunotherapy respectively. Twenty-three(63.89%) had targetable mutations (EGFR Exon 19 or 21, EGFR Exon 20 insertion, ALK, ROS1, MET Exon1 4 skipping, ROS1 or KRAS12C detected either in ct-DNA or tissue). Fifteen (65.21%) out of these 23 started targeted therapy as their 1 st line treatment and of these 8 (53.3%) were initiated on targeted agents prior to availability of tissue NGS reports. Conclusions: Though our TAT for ct-DNA and tissue based NGS testing was similar, ct-DNA based NGS testing enables earlier initiation of targeted treatment for newly diagnosed advanced NSCLC patients with targetable mutations. In the real world, this increases access to targeted agents and may translate to a subsequent improvement in survival outcomes.