Abstract
Circulating tumor DNA (ctDNA)-based molecular profiling is rapidly gaining traction in clinical practice of advanced cancer patients with multi-gene next-generation sequencing (NGS) panels. However, clinical outcomes remain poorly described and deserve further validation with personalized treatment of patients with genomic alterations detected in plasma ctDNA. Here, we describe the outcomes, disease control rate (DCR) at 3 months and progression-free survival (PFS) in oncogenic-addicted advanced NSCLC patients with actionable alterations identified in plasma by ctDNA liquid biopsy assay, InVisionFirst®-Lung. A pooled retrospective analysis was completed of 81 advanced NSCLC patients with all classes of alterations predicting response to current FDA approved drugs: sensitizing common EGFR mutations (78%, n = 63) with T790M (73%, 46/63), ALK / ROS1 gene fusions (17%, n = 14) and BRAF V600E mutations (5%, n = 4). Actionable driver alterations detected in liquid biopsy were confirmed by prior tissue genomic profiling in all patients, and all patients received personalized treatment. Of 82 patients treated with matched targeted therapies, 10% were at first-line, 41% at second-line, and 49% beyond second-line. Acquired T790M at TKI relapse was detected in 73% (46/63) of patients, and all prospective patients (34/46) initiated osimertinib treatment based on ctDNA results. The 3-month DCR was 86% in 81 evaluable patients. The median PFS was of 14.8 months (12.1–22.9m). Baseline ctDNA allelic fraction of genomic driver did not correlate with the response rate of personalized treatment (p = 0.29). ctDNA molecular profiling is an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients. Clinical outcomes with targeted therapies endorse the use of liquid biopsy by amplicon-based NGS ctDNA analysis in first line and relapse testing for advanced NSCLC patients.
Highlights
Since the identification of driver oncogenic alterations in advanced non-small cell lung cancer (NSCLC), tumor genomic profiling is standard of care in daily clinical practice
Patients were included in the analysis if they met the following criteria: 1) stage IIIB/IV NSCLC, with a positive InVisionFirst1-Lung circulating tumor DNA (ctDNA) liquid biopsy for an Clinical outcomes in advanced NSCLC patients with liquid biopsy genomic profiling actionable alteration with or without concurrent tissue biopsy, and 2) treated with an appropriate targeted therapy, namely Food and Drug Administration (FDA)-approved tyrosine kinase inhibitors (TKI) according to the mutation identified
The objectives of the study were to evaluate the disease control rate (DCR) at 3 months in patients treated with matched targeted therapies according to InVisionFirst1-Lung results, progression free survival (PFS) on TKI treatment and assess the correlation between baseline allele fraction (AF) in ctDNA and clinical outcomes
Summary
Since the identification of driver oncogenic alterations in advanced non-small cell lung cancer (NSCLC), tumor genomic profiling is standard of care in daily clinical practice. Rebiopsy at the time of TKI progression is not always feasible nor informative [4], leading to significant numbers of patients being under-genotyped or non-genotyped for genomic biomarkers recommended by professional guidelines [5] These clinical guidelines, including an expert committee convened by the International Association for the Study of Lung Cancer (IASLC), advocate comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) technology by circulating tumor DNA (ctDNA) testing at baseline or at the time of progression to personalized treatment when tissue biopsy is infeasible or inadequate for molecular analysis [6]. The differentiation of performance between liquid biopsy assays highlights the importance of the choice of tests being used in clinical practice that require robust analytical and prospective clinical validation data [11]
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