Pretreatment ctDNA levels may predict survival in neoadjuvant-treated NSCLC patients
medwireNews: Assessing circulating tumor (ct)DNA levels prior to initiating neoadjuvant chemoimmunotherapy for locally advanced non-small-cell lung cancer (NSCLC) could help to identify patients likely to derive long-term benefit from treatment, suggest exploratory data.
The findings were presented by Atocha Romero (Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain) at the IASLC 2021 World Conference on Lung Cancer.
“Currently there are no biomarkers available to identify patients who exhibit long-term benefit from chemoimmunotherapy-based treatment,” but “pretreatment levels of circulating tumor DNA have been shown to be an important prognostic factor in other scenarios” such as metastatic EGFR-positive NSCLC, she explained at a press briefing.
The team therefore conducted an exploratory analysis of the phase 2 NADIM trial that evaluated neoadjuvant nivolumab plus chemotherapy in 46 patients with resectable stage IIIA NSCLC to investigate the value of ctDNA in this setting.
Of the 43 participants with available pretreatment blood samples, nearly three-quarters (69.8%) tested positive for ctDNA using the Oncomine Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific, Waltham, Massachusetts, USA).
As reported by Romero, patients with low ctDNA levels – defined as a sum of the mutant allele frequency (MAF) below 1% – had significantly better progression-free survival (PFS) and overall survival (OS) than those with higher levels, at hazard ratios of 0.22 and 0.04, respectively, in multivariate analysis.
The results were similar when using other criteria, such as a cutoff of 2% for the sum MAF or of 1% for MAF max, which takes into account the most frequently detected mutation.
By contrast, there was no significant association between clinical response as assessed by the RECIST criteria and either PFS or OS.
For ctDNA, the adjusted C-statistic to predict PFS was 0.68, while it was 0.85 for OS – these values were better than those for RECIST clinical response, at 0.61 and 0.68, respectively, said Romero.
And she summarized: “Pretreatment circulating tumor DNA levels can identify patients at high risk of progression and outperformed radiological response assessed according to RECIST criteria in the prediction of survival.”
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