Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors

Paul van der Leest, Birgitta Hiddinga, Anneke Miedema, Maria L Aguirre Azpurua, Naomi Rifaela, Arja Ter Elst, Wim Timens, Harry J M Groen, Léon C van Kempen, T Jeroen N Hiltermann, Ed Schuuring*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

19 Citaten (Scopus)
88 Downloads (Pure)

Samenvatting

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.1 criteria, progression-free survival (PFS), DCB, and overall survival (OS). To this aim, blood tubes were collected from advanced-stage lung adenocarcinoma patients (n = 100) receiving immune checkpoint inhibitors (ICI) at baseline (t(0)) and prior to first treatment evaluation (4-6 weeks; t(1)). Nontargetable (driver) mutations detected in the pretreatment tumor biopsy were used to quantify tumor-specific ctDNA levels using droplet digital PCR. We found that changes in ctDNA levels were strongly associated with tumor response. A > 30% decrease in ctDNA at t(1) correlated with a longer PFS and OS. In total, 80% of patients with a DCB of >= 26 weeks displayed a > 30% decrease in ctDNA levels. For patients with a PD-L1 tumor proportion score of >= 1%, decreasing ctDNA levels were associated with a higher frequency a DCB (80%) and a prolonged median PFS (85 weeks) and OS (101 weeks) compared with patients with no decrease in ctDNA (34%; 11 and 39 weeks, respectively). This study shows that monitoring of ctDNA dynamics is an easy-to-use and promising tool for assessing PFS, DCB, and OS for ICI-treated NSCLC patients.

Originele taal-2English
Pagina's (van-tot)2910-2922
Aantal pagina's13
TijdschriftMolecular oncology
Volume15
Nummer van het tijdschrift11
Vroegere onlinedatum25-sep.-2021
DOI's
StatusPublished - nov.-2021

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