The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to researchers, highly concordant results were observed when estimates of the tumor mutational burden (TMB) in specimens of non-small cell lung cancer (NSCLC) were made using 3 different targeted exome next-generation sequencing (NGS) assays. The findings from this study were presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.

Tumor mutational burden (TMB), defined in this study as the number of synonymous (ie, mutations that do not alter protein sequence) and nonsynonymous (ie, mutations that alter protein sequence) gene mutations per megabase of DNA within the coding region of the tumor genome, is an emerging biomarker for the prediction of patients with cancer likely to respond to immune checkpoint inhibitor therapy. 

Related Articles

Although assessments of TMB can be determined using a number of commercially available NGS assays, uncertainty exists regarding the level of concordance between them due to variability in the number and specific types of genes included in each respective gene panels, as well as the different informatics algorithms used in the interpretation of results. 

In this study, estimates of TMB obtained with 2 different targeted exome NGS panels, TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutational Load (TML), were compared with those from the FoundationOne CDx (F1CDx) targeted exome-sequencing panel using 96 tumor tissue specimens available from clinically annotated patients with early-stage NSCLC.

For the overall set of samples, a high level of concordance in TMB determinations from the TSO500 assay (R2 = .8775) and the TML assay (R2 = .8119), both compared with the F1CDx assay, was observed.

A comparison of TMB determinations made using the TSO500 and TML assays also revealed concordant results (R2 =.8545).

Interestingly, a higher level of concordance with respect to TMB was observed between the TSO500 (R2 =.9120) and the TML (R2 = .8768) assays as compared with the F1CDx assay when only the subset of specimens (55 specimens) with a low level (less than 1%) of programmed cell death-ligand 1 (PD-L1) expression was considered.  Conversely, a lower level of concordance compared with the F1CDx assay was seen (ie, R2 = .7466 [TSO500]; R2 = .5735 [TML]) for the subset of specimens (41 samples) with a PD-L1 expression level of 1% or higher. 

The study authors also noted that the TSO500 and TML assays had a lower range of TMB values for those samples classified as TMB-high by the F1CDx assay, leading them to suggest that a lower low/high TMB cutoff may be necessary for the TSO500 and TML assays.  

Read more of Cancer Therapy Advisor‘s coverage of ESMO Congress 2019 by visiting the conference page.

Disclosure: This study was funded by Bristol-Myers Squibb. The study authors reported receiving financial support from pharmaceutical companies; for a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.

Reference

Garrido-Martin EM, Ramos-Paradas J, Hernandez-Prieto S, et al. Harmonization study of tumour mutational burden determination in non-small cell lung cancer (NSCLC). Presented at: European Society for Medical Oncology Congress 2019. September 27-October 1, 2019. Barcelona, Spain. Abstract LBA17.