Circulating Tumor DNA Monitoring on Chemo-immunotherapy for Risk Stratification in Advanced Non–Small Cell Lung Cancer

Abstract

Purpose: Chemoimmunotherapy (chemoIO) is a prevalent first-similar ctDNA dynamics were noted across treatment arms line treatment for advanced driver-negative non–small cell lung during chemoIO. ctDNA decrease from baseline to C4D1 was cancer (NSCLC), with maintenance therapy given after induction. associated with improved outcomes across multiple cutoffs for However, there is significant clinical variability in the duration, patients treated with chemoIO. When including patients with dosing, and timing of maintenance therapy after induction chemoIO. missing plasma or ctDNA- at baseline, patients with ctDNA- at We used circulating tumor DNA (ctDNA) monitoring to inform C4D1 (clearance), had more favorable progression-free survival outcomes in patients with advanced NSCLC receiving chemoIO. (median 8.8 vs. 3.5 months; HR, 0.32;0.20–0.52) and OS (median Experimental Design: This retrospective study included 221 not reached vs. 8.9 months; HR, 0.22; 0.12–0.39) from C4D1 than patients from a phase III trial of atezolizumabþcarboplatinþnabctDNAþ patients. paclitaxel versus carboplatinþnab-paclitaxel in squamous NSCLC Conclusions: ctDNA monitoring during induction chemoIO (IMpower131). ctDNA monitoring used the FoundationOne can inform treatment outcomes in patients with advanced Tracker involving comprehensive genomic profiling of pretreatNSCLC. Importantly, monitoring remains feasible and informent tumor tissue, variant selection using an algorithm to exclude mative for patients missing baseline ctDNA. ctDNA testing nontumor variants, and multiplex PCR of up to 16 variants to detect during induction chemoIO identifies patients at higher risk and quantify ctDNA. for disease progression and may inform patient selection Results: ctDNA was detected (ctDNAþ) in 96% of pretreatfor novel personalized maintenance or second-line treatment ment samples (median, 93 mean tumor molecules/mL), and strategies.