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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Outcomes in oncogenic-addicted advanced NSCLC patients with actionable mutations identified by liquid biopsy genomic
Jordi Remon1, Aurelie Swalduz2, David Planchard1
1Department of Cancer Medicine, Gustave Roussy, Villejuif, France.
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.
Insights
Circulating tumor DNA (ctDNA) liquid biopsy accurately identifies actionable mutations in advanced non-small cell lung cancer (NSCLC). Personalized treatment based on ctDNA results shows promising disease control and progression-free survival in NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Circulating tumor DNA (ctDNA)-based molecular profiling is increasingly used for advanced cancer patients.
- Clinical outcomes of ctDNA-guided personalized treatment require further validation.
Purpose of the Study:
- To describe outcomes, disease control rate (DCR), and progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients with actionable alterations detected by ctDNA liquid biopsy.
- To validate the use of ctDNA liquid biopsy for personalized treatment in NSCLC.
Main Methods:
- Pooled retrospective analysis of 81 advanced NSCLC patients.
- Actionable alterations identified using the InVisionFirst®-Lung ctDNA assay.
- Patients received personalized treatment based on detected genomic alterations (EGFR, ALK/ROS1, BRAF V600E).
- Next-generation sequencing (NGS) panels were used for ctDNA analysis.
Main Results:
- 86% 3-month disease control rate (DCR) in 81 evaluable patients.
- Median progression-free survival (PFS) of 14.8 months.
- Acquired T790M mutation detected in 73% of EGFR-mutated patients, leading to osimertinib treatment.
- No correlation between baseline ctDNA allelic fraction and treatment response (p = 0.29).
Conclusions:
- ctDNA molecular profiling is accurate and reliable for detecting clinically relevant alterations in advanced NSCLC.
- Personalized treatment guided by ctDNA liquid biopsy demonstrates favorable clinical outcomes.
- Endorses the use of ctDNA liquid biopsy for first-line and relapse testing in advanced NSCLC.
