481P - Comparative analysis of three NGS platforms assessing tumor mutational burden and mutational landscape in resectable non-small cell lung cancer

Background

Identifying actionable driver mutations via tissue-based comprehensive genomic profiling (CGP) is paramount in treatment decisions for metastatic non-squamous, non-small cell lung cancer (NSCLC). Here, we elucidate the feasibility of CGP in early-stage NSCLC, and compare the tumor mutational burden (TMB) and mutation landscape using three different platforms.

Methods

Surgically resected NSCLC samples (N=96) collected between October 2011 and April 2020 at Yonsei Cancer Center were analyzed using whole-exome sequencing (WES) (Illumina DRAGEN, v3.8) (N=96), TruSight Oncology 500 (TSO500, v2.0) (for research use only) (Illumina) (N=96), and Foundation One CDx Assay (F1CDx) (N=26) to assess the concordance in TMB calculation and targetable mutations. Programmed death-ligand 1 (PD-L1) expression were evaluated using Vectra Polaris (Akoya).

Results

The stage distribution after surgery was 80% I (N=77) and 20% II (N=19). Ninety-nine percent (N=95) were adenocarcinoma. All 96 samples were analyzed with WES and TSO500. Among these samples, 26 samples were analyzed with F1CDx. The median TMB with WES and TSO500 was 1.57 and 4.7 mut/Mb, respectively (p<0.05). The median TMB was 1.88, 5.5, 4 mut/Mb for WES, TSO500 and F1CDx, respectively (p=0.0048). Linear regression analysis of TMB values calculated using concordance correlation coefficient (CCC) between WES and TSO500 resulted in a R²=0.76. For PD-L1 tumor proportion score (TPS) of <1% (negative, N=18), ≥1% (low, N=68) and ≥ 50% (high, N=10), the CCC were 0.075, 0.79, and 0.95, respectively. The CCC values for TMB concordance were variable between 3 platforms (WES vs. TSO500, R²=0.87; WES v. F1CDx, R²=0.72; TSO500 vs. F1CDx, R²=0.84). Mutation landscape revealed EGFR mutation (51%, N=49) as the most common actionable driver mutation, comprising of L858R (N=22), E19del (N=20), and other non-common EGFR mutations (N=7).

Conclusions

F1CDx and TSO500 showed robust analytical performance for TMB assessment with TSO500 showing stronger concordance of TMB with high PD-L1 expression. As paradigm for early-resected NSCLC continues to evolve, understanding TMB and mutation landscape may help advance clinical outcomes for this subset of patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yonsei Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.