395P - Molecular landscape of Indian NSCLC: Is NGS the answer?

Background

The list of therapeutically relevant biomarkers in NSCLC is continually expanding and hence molecular profiling is of paramount importance. Tissue availability and chance of rebiopsy is a major limitation in lung cancer and sequential single gene assays lead to tissue exhaustion and inadvertent delays in institution of therapy. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape in an Indian NSCLC cohort.

Methods

414 consecutive patients who underwent both single gene assay and NGS were included in the study. The NGS panel is a custom made 34 gene panel interrogating for canonical alterations in genes implicated in lung carcinoma, including both DNA and RNA based assays A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted.

Results

414 samples were evaluated. Median age was 69 years, 52 % were male, 59 % were never smokers, 92.3 % had stage IV disease and 97.9 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (36.2 %), KRAS (30.6 %), BRAF (5.8 %) and ERBB2 (5.9 %) mutations were found. RNA fusion testing revealed fusions in ALK (6.2 %), RET (5.9 %) and ROS1 (2.1 %). Compared to sequential testing in EGFR, ALK and ROS1 negative patients, upfront NGS testing resulted in an additional 1.2 % of patients with actionable alterations for targeted therapy being identified. However the turnaround time for NGS was a median 14.2 days and cost increment was 19%. However, detection of complex EGFR alterations, variant ALK fusions, and ROS1 fusions also improved by 5.2%, 1.5% and 3.4% respectively. Additionally squamous histology patients also depicted MET exon 14 skipping and KRAS G12C alterations in 2.4% and 4.7% cases, respectively.

Conclusions

This study underscores the need for upfront NGS testing despite increment in expenditure for the patient. Our results support the implementation of diagnostic NGS in NSCLC to allow patients access to the most appropriate molecularly targeted therapy. In addition, we also advocate performing panel based upfront NGS testing in patients with squamous histology as well, especially in the light of recent approvals of capmatinib and sotorasib fro MET exon 14 skipping and KRAS G12C alterations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ullas Batra.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.