Genomic alterations profiling by liquid biopsy and their association to immune checkpoints inhibitors (ICI) response in a cohort of non-small cell lung cancer (NSCLC) patients.

Abstract

e21524 Background: In metastatic NSCLC, identification of biomarkers of response to immune checkpoint inhibitors (ICI) is still an unmet need. Liquid biopsy, including the detection of circulating tumor DNA (ctDNA) in patients’ bloodstream, is an emerging tool for detecting and monitoring genetic alterations. Mutations in specific genes as KRAS or STK11, in combination with PDL1, have been suggested as potential biomarkers to select responders to ICI. Methods: Digital NGS of ctDNA was analyzed by Guardant360 in samples from 89 patients with advanced NSCLC treated with ICI between 2017 to 2019. Plasma samples after progression to ICI were obteined from 40 patients and we focus in this subgroup to explore mutations of genes commonly alterated in lung cancer and correlate them with clinical outcomes. Results: Forty patients were included in the analysis with a median age of 64.5 years and 62.5% were diagnosed with adenocarcinoma. Fourteen patients were treated with single agent ICI as first line, 19 patients as second line and 7 in third line. A median of 4 mutations per patient were detected (range 0-13). Mutations (mut) in TP53 were found in 85% of the patients, KRAS in 34%, STK11 in 22% and both genes KRAS and STK11 were alterated in 12.5% of the patients. Globally, median PFS (mPFS) of the patients treated with ICI was 7.5 months. mPFS in patients harboring KRAS mutations was 4.9 m ( vs 10.1 m in patients without KRASmut, logrank test p-value = 0.031) and 4.1 m in those patients with STK11 mutations (vs 9.5 m in patients without STK11mut, logrank test p-value = 0.034). Additionally, mutations in both genes were also associated to statistically significant shorter mPFS 3.9 m vs 9.5 m (logrank test p-value < 0.01). Conclusions: Our results support the idea that tumor alterations identified by liquid biopsy panels can potentially contribute as biomarkers of response to ICI in NSCLC. When analyzing the mutational panorama after ICI treatment, we find that those patients exhibiting KRAS and/or STK11 mutations in their ctDNA have a shorter PFS.