Changes in tumor mutational burden in serially biopsied non-small cell lung cancer.

Abstract

e14286 Background: High tumor mutational burden (TMB) has been associated with response to checkpoint blockade in non-small cell lung cancer (NSCLC) and other malignancies. However, the degree to which TMB changes over time, across anatomical sites, and with intervening treatment remains unknown. To evaluate TMB changes across time points, we compared TMB in tissue specimens from patients with serially-biopsied NSCLC. Methods: Clinicopathologic characteristicsand changes in TMB were analyzed from patients with NSCLC and more than one biopsy that had undergone targeted next generation sequencing (NGS, OncoPanel) at the Dana-Farber Cancer Institute. Those representing distinct primary tumors by histology and/or discordant mutational profiles were excluded. Results: 134 NSCLC patients with more than one interpretable NGS result were identified; 23 were excluded due to separate primary tumors. Of the 111 remaining patients included in the analysis, the median time between samples was 14 months (range: 0 to 114 months). TMB correlated closely across all matched tumor pairs (Pearson’s r = 0.89), and greater variability in TMB was seen in biopsies taken from different anatomic sites (p = 0.04) compared to biopsies obtained from the same lesion. There was no significant change in median TMB with any intervening therapy, as TMB increased in some patients and decreased in others. Conclusions: In this observational study, TMB correlated closely across tumor pairs. However, these data suggest that sampling from different tumor sites may be associated with greater discrepancies in TMB. It is possible these differences could account for challenges in using TMB as a predictive biomarker for immunotherapy response. Further prospective investigation is needed to inform decisions regarding the need for repeat biopsy in patients starting immunotherapy with remote tissue samples.