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

Pellini, B., et al. Circulating Tumor DNA Monitoring on Chemo-immunotherapy for Risk Stratification in Advanced Non-Small Cell Lung Cancer. Clinical Cancer Research. September 13, 2023. https://doi.org/10.1158/1078-0432.CCR-23-1578

Chemo-immunotherapy (chemoIO) is an established first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance immunotherapy given following chemoIO induction treatment. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after chemoIO. Circulating tumor DNA (ctDNA) monitoring technologies have the promise to support oncologists in treatment decision making for this patient population following chemoIO.

Researchers utilized ctDNA monitoring for risk stratification in advanced squamous NSCLC receiving chemoIO. This retrospective study included 221 patients from a completed phase III trial, IMpower131. ctDNA monitoring was conducted utilizing FoundationOne®Tracker, which involved comprehensive genomic profiling of pre-treatment tumor tissue, variant selection using an algorithm to exclude non-tumor variants, and multiplex PCR/next generation sequencing of up to 16 variants to detect and quantify ctDNA.

ctDNA was detected in 96% of pre-treatment samples, and similar ctDNA dynamics were noted across treatment arms during chemoIO. ctDNA decrease from baseline to the landmark timepoint at cycle 4, day 1 (C4D1) was associated with improved outcomes for patients treated with chemoIO. When including patients with missing plasma or at baseline, patients with ctDNA (clearance) at C4D1 had more favorable progression-free survival and overall survival from C4D1 than ctDNA positive patients.

ctDNA monitoring during chemoIO can stratify risk in patients with advanced NSCLC. Importantly, monitoring remains feasible and informative for patients missing baseline ctDNA. ctDNA testing during chemoIO may offer an opportunity to identify patients at higher risk for disease progression and inform patient selection for novel personalized maintenance strategies.

View the full publication in Clinical Cancer Research.