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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Wednesday, December 4, 2024
An article published in npj Precision Oncology has highlighted the use of liquid biopsy to predict biomarkers for immunotherapy in patients with advanced non–small cell lung cancer (NSCLC). Andrea Boscolo Bragadin, PhD, of the Veneto Institute of Oncology IOV-IRCCS, Padua, Italy, and colleagues performed a prospective study in patients treated with single-agent immune checkpoint inhibitors (ICIs). They integrated clinicopathologic features and results of circulating tumor DNA (ctDNA) monitoring to build a predictive model.
“To shed light on heterogeneity in clinical benefit, several biomarkers have been investigated, and, overall, findings suggest that response to immunotherapy is likely not related to a single biomarker but rather to the dynamic interaction among factors related to host, tumor, and microenvironment,” stated Dr. Bragadin and colleagues.
A total of 113 patients with advanced NSCLC treated with ICIs were included in this study. Liquid biopsies were performed at the start of treatment (T1), after 3 weeks of treatment (T2), and at the time of radiologic evaluation (T3). Collected plasma samples were then used for cfDNA extraction and quantity/quality assessment. Genomic DNA was also extracted and used to perform next-generation sequencing.
Findings revealed that molecular variables were associated with outcome endpoints, and multivariate analysis revealed that PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2–T1), and T2 variant allele frequency (VAF) were associated with shorter progression-free survival. Additionally, PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2–T1) increase, and T2 maxVAF affected overall survival, whereas high PD-L1 expression in the first-line setting, elevated T2 maxVAF, and cfDNA increase (∆T2–T1) correlated with worse progression-free survival. Moreover, higher T2 maxVAF and cfDNA increase (∆T2–T1) correlated with worse overall survival.
“Predicting the clinical benefit of immunotherapy in advanced NSCLC is recognized as one of the main challenges for clinical and translational research in oncology,” the investigators commented. “Our integrated model warrants further validation as a tool to customize treatment in nononcogene-addicted NSCLC.”
Disclosure: The study authors reported no conflicts of interest.
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