P3.02c-054 Prognostic Role of cfDNA in Patients with NSCLC under Treatment with Nivolumab: Topic: IT

Abstract

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor approved for previously treated advanced non-small cell lung cancer (NSCLC). Liquid biopsy is a non-invasive blood test that detects cell-free DNA (cfDNA) shed from the tumour into the bloodstream. Monitoring cfDNA in patients with NSCLC under treatment with Nivolumab may be helpful to assess efficacy of the therapy and may be related with patients’ survival. Peripheral blood samples were obtained from 74 patients with pretreated advanced NSCLC within a single-institutional translational research trial from May 2015 to April 2016. Patients received intravenous Nivolumab at 3 mg/kg every 2 weeks until progression or unacceptable toxicity. All the patients underwent CT-scan every 4 cycles and responses were classified according to immune related Response Criteria. CfDNA was extracted from plasma using the Circulating Nucleic Acid Kit (Qiagen). The quantification of cfDNA (ng/ml plasma) was performed by qPCR using hTERT single copy gene. Kaplan-Meier survival function was used to compare the survival curves from cfDNA at baseline and at the time of first evaluation (after 4 cycles of Nivolumab). Among the 74 enrolled patients 72 were evaluable for cfDNA survival analyses; 14 experienced early death, 25 progressive disease (PD), nine partial response (PR),19 stable disease (SD) and five were not evaluable for response. 27 out of the 28 responsive patients (PR+SD) are still alive at the time of analysis. In 25 evaluable patients with PD after the first radiological evaluation, median cfDNA < 786 ng/ml was significantly associated with an improved median survival as compared to cfDNA ≥786 ng/ml (295 vs 96 days respectively, HR=0.09290, 95% CI 0.019987-0.4322, p-value: 0.0052); similar results have been obtained in the subset of 25 patients progressing at best response (p-value: 0.0042). Analyzing the OS of the 72 evaluable patients, median survival of those with cfDNA<786 ng/ml is still undetermined, while it is equal to 181 days for those with cfDNA>786 ng/ml (HR 0.3559, 95%CI 0.1674-0.7568, p-value 0.0035). Our preliminary data show a significantly improved survival for NSCLC patients treated with Nivolumab having cfDNA<786 ng/ml than those with higher cfDNA; the correlation with OS is observed in patients at the first radiological evaluation and in those with PD at best response.