3295 - Clinical impact of plasma Next-Generation Sequencing (NGS) in advanced Non-small cell lung cancer (aNSCLC)

Background

NGS provides genetic information with potential impact on clinical practice. Plasma NGS has the advantage to reduce the need to repeat biopsy and provide information about tumor heterogeneity.

Methods

Since March 2018 we prospectively screened aNSCLCs consecutively referring to our institution for potential eligibility to VISION trial (NCT02864992). All the patients (pts) were previously screened for EGFR/ALK/ROS1 sensitizing alterations according to standard methods and positive cases were excluded. NGS was performed with METex14 Guardant360® covering 73 genes including all somatic alterations recognized as potential targets by NCCN. A parallel cohort of pts was also analysed with NGS in tissue by using METex14 Oncomine™ Focus Assay (MolecularMD) covering 59 genes. All identified druggable genetic alterations were tested for confirmation with a different method.

Results

We included 159 pts, 91 (57%) male, 37 (23,3%) smokers and 81 (50,9%) former smokers. Histology was: 144 adenocarcinoma, 7 squamous cell carcinoma, two sarcomatoid and 6 large cell/undifferentiated. 129 (81%) cases were analyzed in plasma and 63 (49%) had tissue NGS results for comparison. Median number of detected genetic alterations was 2 and maximum number was 17. No alterations were found in 14 cases (11%). Two of them were then retested and became positive. We found 34 (26%) potentially druggable genetic alterations and three of them showed discordant results between tissue and plasma. Among all druggable genetic alterations, till now we have treated 12 pts with targeted agents and six had already radiological response evaluable: five of them obtained control of disease. 18 pts with druggable alterations had already received immunotherapy (IT) and only two of them obtained objective response: METex14 mutation and RET rearrangement. We also found 5 cases of KRAS-STK11 co-mutations, three were treated with IT and no response was recorded. In parallel, 89 (56%) cases were analyzed in tissue and 44 (49%) were evaluable for NGS. Ten (23%) potentially druggable genetic alterations were found.

Conclusions

Plasma NGS was feasible and provided additional information: new druggable genetic alterations were found and potential impact of NGS on response to IT emerged.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Istituto Oncologico Veneto, IOV IRCCS.

Funding

Merck KGaA.

Disclosure

All authors have declared no conflicts of interest.