Abstract 5960
Background
Next generation sequencing (NGS) of cfDNA in NSCLC is entering in clinical practice. Several commercially available platforms using NGS report wide variety of somatic aberrations. Vendors also include therapeutic suggestions to guide oncologists. In addition, new levels of evidence tools are now available for tissue results, but not still used in LB.
Methods
Advanced NSCLC pts underwent commercial 73-gene cfDNA NGS analysis. ESMO Scale for Clinical Actionability (ESCAT) and OncoKB were used to grade levels of evidence for categorize aberrations and compared with variant allele frequency (VAF), treatment decisions, and vendor suggestions.
Results
77 samples from 73 advanced NSCLC pts (73% adenocarcinoma, 27% squamous cell carcinoma) at the time of diagnosis (49%) or during disease course (51%) were analyzed. Median turnaround time was 8 days (range 5-17), with no genotyping failures. There were 323 unique somatic alternations identified: Sequence mutations (254), amplifications (43), synonymous mutations (23), and fusions (3). Median cfDNA % was 0.7 (range 0.05-49.5); 7 samples had no detectable genetic alterations. Variants of unknown significance were 33% of point mutations. We detected 87 and 88 potentially actionable genetic alterations according to ESCAT (IA-IV) and OncoKB (1-4), respectively, and 26% received a matched targeted drug. Discrepancies between these two tools and vendor suggestions were reported in 4 cases. We performed a subset analysis of 64 samples: Median VAF was 4.37 % (range 0.16-43.05) and a VAF < 1% was reported in 16 samples; 45% of alterations (excluding amplifications) were clonal events (cfDNA% divided by VAF > 0.5). Among EGFR and ALK positive samples median VAF was 7.98% (range 0.29-41.2); 3/17 samples presented a VAF below 1%, with no detrimental effect on treatment response.
Conclusions
The application of ESCAT and OncoKB is feasible in LB. Driver mutations with low VAF are amenable to receive treatment. VAF could be included as complementary tool to grading systems to better understand the significance of aberrations.Discrepancies between vendor therapeutic suggestions and evidence-based grading systems requests caution in the use of information outside the molecular tumor board.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C.D. Rolfo: Honoraria (self), personal fees : Novartis; Honoraria (self), personal fees : MSD; Non-remunerated activity/ies, non-financial support : OncoDNA; Honoraria (self), personal fees and non-financial support : GuardantHealth. All other authors have declared no conflicts of interest.
Resources from the same session
2185 - Sequential treatment with afatinib followed by 3rd generation EGFR-TKI – subgroup analysis of the GIDEON trial: a prospective non-interventional study (NIS) in EGFR mutated NSCLC patients in Germany
Presenter: Wolfgang Brückl
Session: Poster Display session 1
Resources:
Abstract
1524 - Effectiveness of sequencing TKIs in patients with EGFR mutation-positive Non-small-Cell Lung Cancer (NSCLC): A French National medico administrative claim database analysis
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
5733 - Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: A multicenter trial of the Korean Cancer Study Group (LU17-19)
Presenter: Tae Min Kim
Session: Poster Display session 1
Resources:
Abstract
5440 - Different stories for different EGFR exon 19 deletion variants
Presenter: Chao Zhao
Session: Poster Display session 1
Resources:
Abstract
2982 - Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy
Presenter: Yuan-Kai Shi
Session: Poster Display session 1
Resources:
Abstract
4002 - Afatinib followed by osimertinib in patients with EGFR mutation-positive (EGFRm+) advanced NSCLC: updated data from the GioTag real-world study
Presenter: Maximilian Hochmair
Session: Poster Display session 1
Resources:
Abstract
2941 - Treatment patterns of EGFR mt+ NSCLC IV pts: Real world data of the NOWEL network
Presenter: Julia Roeper
Session: Poster Display session 1
Resources:
Abstract
4154 - TP53 mutations predicts worse prognosis in EGFR-mutated NSCLC patients receiving TKIs in first- or further line of treatment
Presenter: Matteo Canale
Session: Poster Display session 1
Resources:
Abstract
1175 - HER3 ligand heregulin expression and clinical implication in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors
Presenter: Kimio Yonesaka
Session: Poster Display session 1
Resources:
Abstract
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract