CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors

Filippo G Dall'Olio; Francesca Abbati; Francesco Facchinetti; Maria Massucci; Barbara Melotti; Anna Squadrilli; Sebastiano Buti; Francesca Formica; Marcello Tiseo; Andrea Ardizzoni

doi:10.1177/1758835920952994

CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors

Ther Adv Med Oncol. 2020 Oct 31:12:1758835920952994. doi: 10.1177/1758835920952994. eCollection 2020.

Affiliations

¹ Policlinico Sant'Orsola Malpighi, Division of Oncology, University of Bologna, Via Giuseppe Massarenti, 9, Bologna, 40138, Italy.
² Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.
³ INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France.
⁴ Medical Oncology Unit, University Hospital of Parma, Parma, Italy.

Abstract

Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit.

Materials and methods: This is a retrospective cohort study including patients with stage IIIB-IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well.

Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 >8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24-2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04-0.33; p < 0.001), and for CYFRA 21-1 (HR 0.19; 95% CI 0.07-0.55; p 0.002).

Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit.

Keywords: CEA; CYFRA; NSCLC; advanced lung cancer; carcinoembryonic antigen; cytokeratin 19 fragment; immune checkpoint; predictive; prognostic; serum tumor markers.