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

Authors

Bruna Pellini
Russell W Madison
Merrida A Childress
Shoshana T Miller
Ole Gjoerup
Jason Cheng
Richard S P Huang
Michael Krainock
Pratyush Gupta
Wei Zou
David S Shames
Solomon Moshkevich
Marcus Ballinger
Minetta C Liu
Amanda Young
Minu K Srivastava
Geoffrey R Oxnard
Mark A Socinski

Publication Date

11-14-2023

Journal

Clinical Cancer Research

Abstract

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor variants, and multiplex PCR of up to 16 variants to detect and quantify ctDNA.

RESULTS: ctDNA was detected (ctDNA+) in 96% of pretreatment samples (median, 93 mean tumor molecules/mL), and similar ctDNA dynamics were noted across treatment arms during chemoIO. ctDNA decrease from baseline to C4D1 was associated with improved outcomes across multiple cutoffs for patients treated with chemoIO. When including patients with missing plasma or ctDNA- at baseline, patients with ctDNA- at C4D1 (clearance), had more favorable progression-free survival (median 8.8 vs. 3.5 months; HR, 0.32;0.20-0.52) and OS (median not reached vs. 8.9 months; HR, 0.22; 0.12-0.39) from C4D1 than ctDNA+ patients.

CONCLUSIONS: ctDNA monitoring during induction chemoIO can inform treatment outcomes in patients with advanced NSCLC. Importantly, monitoring remains feasible and informative for patients missing baseline ctDNA. ctDNA testing during induction chemoIO identifies patients at higher risk for disease progression and may inform patient selection for novel personalized maintenance or second-line treatment strategies.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Circulating Tumor DNA, Carboplatin, Retrospective Studies, Paclitaxel, Immunotherapy, Risk Assessment

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Supplementary Materials

PMID: 37702716