Outcomes in oncogenic-addicted advanced NSCLC patients with actionable mutations identified by liquid biopsy genomic profiling using a tagged amplicon-based NGS assay.

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.

Déclaration de conflit d'intérêts

JR has the following competing interests: Advisory / Speaker: MSD, Boehringer-Ingelheim, Pfizer, BMS, Astra Zeneca; Personal Fees: OSE Imunotherapeutics; Travel: OSE Immunotherapautics, Roche, Astra Zeneca. DP has the following competing interests: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. LM has the following competing interests: Consulting, advisory role: Roche Diagnostics; Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, Accommodations, Expenses: Chugai, Roche; Mentorship program with key opinion leaders: funded by AstraZeneca. ER has the following competing interests: Advisory Board: AstraZeneca, Roche, BMS. MP has the following competing interests: Honoraria for Advisory Boards: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, Clovis Oncology, MSD, Bristol-Myers Squibb, Novartis, AstraZeneca, Takeda; Institutional grants: Roche, AstraZeneca, Chugai, Takeda; Symposiums: Eli Lilly, Roche, AstraZeneca, Pfizer, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Takeda, Chugai. PS has the following competing interests: Research funding from Roche, Astra Zeneca, and Novartis. BB has the following competing interets: Sponsored Research at Gustave Roussy Cancer Center Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. SO-C, LL, CJ, and CL have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.*There are no patents, products in development or marketed products associated with this research to declare.