Brief Report: Clinical Outcomes Using Plasma-Based Molecular Profiling to Guide Treatment Decisions in Patients With Advanced NSCLC and Limited Access to Broad Tissue Testing

Abstract

<h2>Abstract</h2><h3>Background</h3> Next-generation sequencing (NGS) for non-small cell lung cancer (NSCLC) is becoming more widely used, but the rate of testing varies depending on the region. Plasma-based NGS is emerging as either complementary or alternative to standard tissue genotyping in metastatic non-small-cell lung cancer (NSCLC), especially in patients with insufficient tumor tissue or when tissue biopsy is not feasible. <h3>Methods</h3> We conducted a retrospective study of advanced NSCLC patients who underwent plasma-based NGS as part of molecular prescreening for clinical trials in a single institution in Madrid, Spain, between August 2017 and March 2019. We analyzed the frequency of oncogenic drivers detected using plasma-based NGS, the proportion of patients treated with genotype-directed therapy, and survival. <h3>Results</h3> One-hundred and nine patients with advanced NSCLC were included for analysis (median age 63 years [range 27-83], 50% women, 15% never-smokers, 80% adenocarcinoma histology). An additional actionable molecular alteration was detected in plasma in 17/109 pts (16%; <i>EGFR exon 19/21</i>, n=6; <i>METex14</i>, n=4; <i>ALK</i> fusion, n=1; <i>RET</i> fusion, n=2; <i>BRAF V600E</i>, n=2; <i>EGFR</i> exon 20 ins, n=1; <i>HER2</i> exon 20 ins, n=1). 14/19 pts (73%) were subsequently treated with a matched targeted therapy. Median OS was 13.7 months in patients without oncogenic driver alterations detected, and 38.7 months in patients with a driver alteration identified treated with a matched targeted therapy. <h3>Conclusion</h3> Complementary testing with plasma-based NGS can identify additional driver alterations in patients with advanced NSCLC, which may lead to increased access to targeted therapy and better outcomes.