Abstract 1246P
Background
Routine molecular screening of non-small cell lung cancer (NSCLC) patients for actionable mutations is often challenging due to limited tumour material and assay sensitivity. NEOlung, a multi-centric exploratory study evaluated the usefulness of non-invasive liquid biopsy and FFPE based hybrid capture-based next generation sequencing (NGS) assays in the primary diagnostic setting.
Methods
We evaluated 201 blood (cfDNA) samples and tissue isolated DNA from 35 FFPE samples, previously tested negative for EGFR and negative or not at all for KRAS mutations. With the two hybrid-capture-based gene panels NEOplus v1 and NEOliquid v1 in combination with a proprietary bioinformatics, we performed NGS to detect point mutations, small InDels, copy number alterations and selected gene fusions in up to 39 (NEOliquid v1) and 94 (NEOplus v1) genes respectively.
Results
Of the 236 total samples, 23 carried a rare driver event, such as ERBB2 or BRAF activating mutations or ALK- or ROS1-fusion based on pre-screening, while 213 sample (183 blood and 30 FFPE) were previously documented to be negative or untested for ALK, BRAF, EGFR, ERBB2, KRAS, MET, RET, ROS1, NTRK1. In the 213 presumably pan-negative samples, NEOliquid v1 identified driver events in ALK (1), BRAF (10), EGFR (6), RET (2), ROS1 (1), ERBB2 (4), KRAS (31), MET (1) in 56 out of the 183 blood samples. NEOplus v1 identified driver events in NTRK1 (1), ALK (1), EGFR (1), KRAS (6), MET (1), RET (1), ROS1 (1), in 12 out of the 30 FFPE samples.
Conclusions
Of the identified mutations, non-invasive NEOliquid v1 identified 12 (6.6%) samples, while FFPE-sample based NEOplus v1 identified 5 (16.7%) samples with known drug approvals. Furthermore, the detection of actionable EGFR mutations in a pre-screened, potential EGFR-negative cohort might be explained by the lower sensitivity or lack of testing in routine assays, especially with respect to non-classical EGFR mutations such as p.I744_E746delinsMK or p.G719C, p.S768I. In conclusion, we identified an additional 6.6% of patients with druggable alterations using NEOliquid v1 and 16.5% using NEOplus v1 within a presumably negative cohort, which shows the added value of hybrid capture-based NGS assays to identify clinically targetable genomic alterations.
Clinical trial identification
Study Number 2016/01.
Editorial acknowledgement
Legal entity responsible for the study
NEO New Oncology GmbH.
Funding
Pfizer Pharma GmbH.
Disclosure
P. Garrido Lopez: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol (BMS); Advisory/Consultancy: Guardant Health; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Gilead; Speaker Bureau/Expert testimony: Rovi; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Sysmex; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Bayer. M. Forster: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): MSD ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck ; Honoraria (self), Advisory/Consultancy: Achilles; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Guardant Health; Honoraria (self), Advisory/Consultancy: Nanobiotix; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Oxford VacMedix; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: PharmaMar; Honoraria (self), Advisory/Consultancy: Roche ; Honoraria (self), Advisory/Consultancy: Takeda. J. Brinkmann: Full/Part-time employment: Pfizer Pharma GmbH. All other authors have declared no conflicts of interest.