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

Abstract

Background 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. Methods 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 Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient’s withdrawn from the study.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). Results 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). Conclusion 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.

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

“…However, except for PD-L1 tissue expression (>50%) that is used to select advanced NSCLC patients to receive pembrolizumab in the first line setting, no reliable prognostic or predictive marker is presently acknowledged for other ICIs. In this context, in preclinical studies, we found that circulating markers may have significant results [29,95,96]. Moreover, the correlation between PD-L1 expression on CTCs and prognosis of advanced patient cohorts treated with immunotherapy has been explored.…”

Prognostic Relevance of Circulating Tumor Cells and Circulating Cell-Free DNA Association in Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab

“…To date, the role of PD-L1 expression as biomarker in immunotherapy is still controversial [11,29,30], and the identification of reliable indicators that might assess prognosis and efficacy of immunotherapy is being strongly pursued [31,32].…”

An Exceptional Responder to Nivolumab in Metastatic Non-Small-Cell Lung Cancer: A Case Report and Literature Review of Long-Term Survivors

“…Limited data at this time suggest that it may be reasonable to rechallenge patients with immunotherapy upon recurrence [6, 33, 41–44], or treat oligometastatic recurrences with surgery or radiation therapy, with lower threshold to initiate systemic therapy following multiple recurrences or in those with higher burden of disease [6]. Furthermore, increased use of liquid biopsies (such as circulating tumor DNA) [45, 46], tumor markers (such as CEA, CA125) [47, 48], and blood parameters (such as NLR) [46] as biomarkers of response or relapse in ICI-treated patients will further identify early responders, discern CRs from occult disease, and guide therapy in patients with early progression.…”