Patients

This is a retrospective study on a cohort of 283 patients with pathologically proven stage IIIB–IV NSCLC for whom baseline serum tumor markers blood levels were available.

Initially, patients treated with nivolumab or atezolizumab as second or further line of therapy between August 2015 and May 2019 were included in a test set to establish the potential of CEA and CYFRA 21-1 as prognostic factors of outcome in patients treated with immunotherapy and to identify the best cutoff levels. The hypothesis was then validated in a second set that included patients treated with first line pembrolizumab from July 2017 to January 2020.

To determine whether CEA and CYFRA 21-1 levels were generally prognostic or, rather, specifically predictive for immunotherapy benefit, a control cohort of patients with advanced NSCLC treated exclusively with chemotherapy from January 2011 to December 2012 at Bologna University Hospital was also evaluated.

This study was approved by the local ethical committee (‘Comitato Etico Area Vasta Emilia Centro’, Approval number 404/2019). All patients alive at the moment of ethics committee approval had to provide written, informed consent. The committee waived the requirement to obtain informed consent for those who were already dead. The end of the observation period for this study was January 2020.

REMARK guidelines were followed for study design, conduct, analysis and evaluation of results²³

Data on clinical and demographics characteristics including age, sex, number of prior systemic chemotherapies, histological type, PD-L1 expression, performance status based on ECOG scale, smoking history, presence or absence of liver, bone and brain metastasis, and neutrophil, lymphocyte count and each of the serum markers CEA and CYFRA at the beginning of immunotherapy (from day ‒28 to day 1 of the first cycle) and after three cycles (±1) were extracted from medical records.

Median overall survival (OS) was chosen as primary endpoint; disease control rate (DCR) was also analysed. OS was measured from the first ICI administration to death from any cause. Tumor response was assessed by computed tomography (CT) scan according to RECIST version 1.1 criteria. Radiologic assessments were performed with CT scans every 8–12 weeks.