Evaluation of Serum Biomarker CEA and Ca-125 as Immunotherapy Response Predictors in Metastatic Non-small Cell Lung Cancer

Anticancer Res. 2021 Feb;41(2):869-876. doi: 10.21873/anticanres.14839.

Abstract

Background/aim: Treatment options for advanced non-small cell lung cancer (NSCLC) include immunotherapy. Elevated carcinoembryonic antigen (CEA) and cancer antigen 125 (Ca-125) levels are associated with poorer prognoses of resected NSCLC, but currently no predictive biomarkers exist for immunotherapy response. This study evaluated CEA and Ca-125 as predictive biomarkers for immunotherapy efficiency in patients with metastatic NSCLC.

Patients and methods: The single-centre observational retrospective study includes NSCLC stage III/IV patients treated with programmed death-ligand 1 (PD-L1) inhibitors nivolumab or pembrolizumab. The primary study endpoint was treatment response assessed by CT-scan following RECIST-criteria 1.1. CEA/Ca-125 serum values were determined at initiation of treatment and repeated every 2 weeks. Values closest to the day of CT-scan were compared to baseline values.

Results: A total of 136 patients were treated with mono-immunotherapy. Of these, 73 patients were included in the CEA group and 53 patients were included in the Ca-125 group. Baseline CEA and Ca-125 ranged from 8.14 to 5,909 and 1.1 to 4,238 respectively. The sensitivity for Ca-125 as predictor for tumor response was 62.9% (95% CI=61.8%-63.6%), specificity 61.1% (95% CI=60.2%-62.0%), with a positive predictive value (PPV) of 75.9% (95% CI=75.2%-76.7%). For CEA, the sensitivity was 72.0% (95% CI=71.5%-72.5%), specificity 47.1% (95% CI 46.4%-47.8%), with a PPV of 80.0% (95% CI=79.6%-80.4%).

Conclusion: Increased serum CEA might predict tumor progression in NSCLC patients treated with PD-L1 inhibitors. Unconfirmed progression accompanied by increased CEA would support discontinuation of the immunotherapy, while continuation would be advised when serum CEA is not increased.

Keywords: CEA; Ca-125; Immunotherapy; NSCLC; PD-L1.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers / blood
  • CA-125 Antigen / blood*
  • Carcinoembryonic Antigen / blood*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Immunotherapy
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nivolumab / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • CA-125 Antigen
  • Carcinoembryonic Antigen
  • Nivolumab
  • pembrolizumab