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

M G Dal Bello,F Biello,G Rossi,M Tagliamento,R A Filiberti,G Barletta,S Coco,C Maggioni,F Grossi,E Rijavec,S Boccardo,M Mussap,A Alama,I Vanni,C Genova,A M Orengo

doi:10.1186/s12967-019-1828-0

Abstract

BackgroundCEA, 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.MethodsPatients 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 Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient’s withdrawn from the study.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).ResultsA 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).ConclusionThe 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.

Highlights

carcinoembryonic antigen (CEA), CYFRA21-1 and neuronspecific enolase (NSE) are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively
Two randomized Phase III studies have been reported on squamous (CheckMate 017) and non-squamous (CheckMate 057) non-small cell lung cancer (NSCLC) [3, 4] leading to drug approval by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for advanced or metastatic NSCLC after prior chemotherapy
Patients and tumor characteristics Seventy out of 74 patients were evaluable for serum markers and response assessment after 4 cycles of nivolumab (4 patients were excluded from the analysis for hemolyzed baseline samples)

Summary

Introduction

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. Two randomized Phase III studies have been reported on squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC [3, 4] leading to drug approval by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for advanced or metastatic NSCLC after prior chemotherapy This improvement in the management of advanced NSCLC has required the identification of prognostic and/or predictive biomarkers to select the best candidates to immunotherapy and to monitor the tumor response [5]. In the present study we tested the hypothesis that their variation compared to the baseline may act as indicators of treatment efficacy and survival in advanced NSCLC patients treated with nivolumab

Methods

Results

Discussion

Conclusion