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
603 - Mendelian Randomization Study of Alzheimer's Disease and Lung Cancer
Presenter: Huaqiang Zhou
Session: Poster Display session 1
Resources:
Abstract
4462 - Spanish registry of thoracic tumors (TTR): Interim analyses of comorbidities, risk associations, personal and family history of cancer
Presenter: Rafael Lopez Castro
Session: Poster Display session 1
Resources:
Abstract
3957 - Pleural effusion TGF-beta is highly diagnostic and prognostic in malignant pleural mesothelioma
Presenter: Paul Stockhammer
Session: Poster Display session 1
Resources:
Abstract
3583 - Immune microenvironment modulation by p14/ARF in Malignant Pleural Mesothelioma
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4255 - Tumor Treating Fields plus chemotherapy for first-line malignant pleural mesothelioma (MPM): radiological responses in the STELLAR trial
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
1803 - Effects of Tumor Treating Fields (TTFields; 150 kHz) and Cisplatin or Pemetrexed Combination Therapy on Mesothelioma cells In Vitro and In Vivo
Presenter: Mijal Munster
Session: Poster Display session 1
Resources:
Abstract
2660 - Real world use of systemic therapy in elderly patients with malignant pleural mesothelioma (MPM)
Presenter: Susana Cedres
Session: Poster Display session 1
Resources:
Abstract
3150 - Pemetrexed/Cisplatin versus Gemcitabine/Cisplatin as first-line treatment for Egyptian patients with malignant pleural mesothelioma
Presenter: Mohamed Alorabi
Session: Poster Display session 1
Resources:
Abstract
4319 - Accuracy of pathologic evaluation for thymic epithelial tumors in an Italian reference Centre
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
4811 - Comprehensive genomic profiling of thymic carcinoma in a sample Chinese population
Presenter: Baohui Han
Session: Poster Display session 1
Resources:
Abstract