The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients

摘要

CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3?mg/kg every 2?weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient’s withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR?+?PR?+?SD), and survival (PFS and OS). A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR?+?20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction?≥?20% over the baseline was significantly associated with DCR (CEA, p?=?0.021; CYFRA21-1, p??0.001), PFS (CEA, p?=?0.028; CYFRA21-1, p??0.001) and OS (CEA, p?=?0.026; CYFRA21-1, p?=?0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction?≥?20% to predict DCR (p?=?0.002) and PFS (p??0.001). The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.