<p>Serum Tumor Marker Dynamics as Predictive Biomarkers in NSCLC Chemo-Immunotherapy and Mono-Immunotherapy Maintenance: A Registry-Based Descriptive Study</p>

Abstract

Objective To evaluate serum tumor markers (STM) as predictive biomarkers in advanced non-small cell lung cancer (NSCLC) treated with chemo-immunotherapy. Methods Patients having received platinum-based chemo-(CHT) and PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) combination therapy were retrospectively followed. Carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA19-9), cytokeratin-19 fragments (CYFRA 21–1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis. The marker with the highest relative elevation was defined “leading STM”, its change was assessed between CHT-ICI as well as mono-ICI maintenance initiation and the respective subsequent restaging. Corresponding computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST). For CHT-ICI combination and subsequent mono-ICI-maintenance therapy, leading STM and RECIST response were evaluated regarding progression-free (PFS) and overall survival (OS) in Kaplan–Meier analyses. Results Among 80 CHT-ICI patients (41% women, mean age 63 years), median PFS was 5 months (M;4,9), median OS was 15M (10,/). PFS was significantly (p=0.042) longer, when the leading STM had decreased at first restaging under CHT-ICI combination therapy (9M (5,12; n=41) vs 5M (3,6; n=16)). In the 54 (67.5%) patients who received subsequent mono-ICI maintenance therapy, STM decrease was similarly associated with significantly (p<0.001) longer PFS (16M (7,/; n=16) vs 3.5M (2,6; n=22)). Patients with radiologically stable or progressive disease and concomitant leading STM decrease had similar PFS in the CHT-ICI combination phase (4M (3,7; n=16) vs 4.5M (2,6; n=14)), but longer PFS in the mono-ICI maintenance setting (13M (7,16; n=10) vs 3M (2,4; n=17)). Median OS was not reached in most subgroups. Conclusion Leading STM dynamics provide predictive biomarker information additional to radiological response evaluation patients receiving CHT-ICI combination therapy, especially in the mono-ICI maintenance setting.

A retrospective study for prognostic significance of type II diabetes mellitus and hemoglobin A1c levels in non-small cell lung cancer patients treated with pembrolizumab

“…Another study revealed that an increase in CEA levels appeared to predict progression in NSCLC patients treated with ICIs (33). Similar results have also been reported in several other studies (34)(35)(36). We also found that clinical laboratory test markers, such as CRP and albumin levels, had prognostic value in the outcome analyses.…”

The Role of Change Rates of CYFRA21-1 and CEA in Predicting Chemotherapy Efficacy for Non-Small-Cell Lung Cancer

“…The levels of serum CYFRA21-1 and CEA were determined by radioimmunoassay (Cobas® 8000, Roche Diagnostic K.K., Tokyo, Japan, and Chemiluminescent Enzyme Immunoassay System LUMIPULSE® L2400, FUJIREBIO INC., Tokyo, Japan). Based on 95% confidence interval (CI) of Chinese common people, the critical value of normal serum CYFRA21-1 and CEA levels is 3.3 ng/ml and 3.4 ng/ml, respectively [ 17 ]. The change rate of serum CYFRA21-1 level was calculated by the following formula: (CYFRA21‐1 level after first chemotherapy–CYFRA21‐1 level before first chemotherapy)∗100%.…”

Dynamics of Early Serum Tumour Markers and Neutrophil-to-Lymphocyte Ratio Predict Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small-Cell Lung Cancer

“…More recently, a decreased leading STM was similarly associated with longer PFS in NSCLC patients treated with monoimmunotherapy, 17 as well as in those treated with chemoimmunotherapy and monoimmunotherapy maintenance. 35 In the present study, we used a panel of 5 STMs, including CEA, CYFRA 21-1, NSE, CA19-9, and CA125, that were linked to poor outcomes of NSCLC patients to define the leading STM.…”