267P - Genomic landscape of non-small cell lung cancer (NSCLC) in India using circulating tumor DNA (ctDNA) in clinical practice

Background

We investigated the landscape of clinically relevant mutations in ctDNA from NSCLC patients in India tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360®) as part of clinical practice.

Methods

Test requests from patients with a diagnosis of advanced stage “lung cancer” were reviewed. We then excluded cases with neuroendocrine (including small cell), sarcomatoid, and pure squamous histology. Clinically relevant biomarkers were defined as mutations in EGFR, ERBB2, KRAS, BRAF V600E, MET exon 14 skipping or amplification; and ALK, ROS1, RET, or NTRK1 rearrangements. Synonymous mutations and variants of unknown significance were excluded.

Results

Among 120 samples from advanced non-squamous NSCLC patients, 47 were from women and 73 from men; median patient age was 66 years. The median turnaround time was 6 days from sample receipt in laboratory to report. Tumour DNA was detected in 112 samples (93.4%), and among these 57 (50.9%) had at least one clinically relevant biomarker. Mutations in EGFR were the most common (n=32, 28.6%) and included exon 19 deletion (n=19, 60.8%), L858R (n=5, 16%), exon 18 deletion (n=1, 3.2%), exon 20 insertion (n=4, 12.8%), and other pathogenic point mutations (n=6, 19.2%). Compound EGFR mutations occurred in 10 samples, including 4 with a driver mutation and T790M. Other biomarkers included mutations in KRAS (n=4, 3.6%) and ERBB2 (n= 11, 9.8%), rearrangements of ALK (n=2, 1.8%), RET (n=3, 2.7%), MET exon 14 skipping (n=5, 4.5%), and MET focal amplification (n=1, 0.9%). Among 89 samples that lacked commonly tested alterations (EGFR exon 19 deletion, EGFR L858R, ALK fusion or ROS1 fusion), clinically informative alterations were detected in 34 (38.2%). Table: 267P

Summary of alterations detected in advanced NSCLC patients

Conclusions

Clinically relevant biomarkers were detected in more than half of plasma samples from Indian advanced non-squamous NSCLC patients tested with plasma based NGS. Using a single assay, both common and rare mutations could be found in a timely manner (median 6 days turnaround time), obviating the need for multiple tests to identify less common actionable alterations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guardant Health AMEA.

Funding

Has not received any funding.

Disclosure

A.K. Mukherjee, N. Joshi, S. Olsen: Financial Interests, Institutional, Full or part-time Employment: Guardant Health Inc. All other authors have declared no conflicts of interest.