WCLC Sept 2021 | Using liquid biopsy to predict the detrimental effects of ICIs in KRAS-mutant NSCLC

Whilst immune checkpoint inhibitors (ICIs) have dramatically changed outcomes for patients with non-small cell lung cancer (NSCLC), there is a significant heterogeneity in treatment response, with some patients experiencing detrimental effects such as disease hyper-progression and early death. In this video, Laura Bonanno, MD, Istituto Oncologico Veneto, Padova, Italy, gives an overview of the preliminary results of a study examining the role of liquid biopsy as a potential predictor of detrimental effects of ICIs in NSCLC. In a cohort including KRAS-mutated patients, it was found that changes in the KRAS mutant allele fraction (MAF) correlated with patient outcomes and in addition, one case of hyper-progression was associated with a significant increase in the KRAS MAF. Moreover, in a cohort of patients at risk of experiencing hyper-progression and early death, next-generation sequencing (NGS) analyses suggested that early death and hyper-progression are due to different biological phenomena. Additionally, changes in cell-free DNA (cfDNA) were associated with the risk of early death whilst changes in variant allele fraction were associated with the risk of hyper-progression. Dr Bonanno explains that in the clinical setting, it may be beneficial to first quantify cfDNA to exclude patients at a higher risk of early death, and then perform NGS analysis to assess changes in variant allele fraction to identify patients at a higher risk of hyper-progression. This interview took place at the World Conference on Lung Cancer (WCLC) 2021.