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Introduction
Lung cancer remains the leading cause of cancer death globally. Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, has been shown to confer a survival benefit over docetaxel for patients with previously treated squamous or non-squamous non–small cell lung cancer (NSCLC).1,2 In Japan, nivolumab is approved for use in patients with either squamous or non-squamous NSCLC regardless of their PD-L1 expression level.
CYFRA 21-1 is a prognostic marker for NSCLC,3 and lung squamous cell carcinomas (SCCs) show elevated values compared with other histological types. A low CYFRA 21-1 level has also been reported as a predictor of the response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in EGFR-mutated NSCLC patients4 and is regarded as a potential independent prognostic factor, along with the EGFR mutation status.5 According to recent phase III studies, a squamous histology predicts the efficacy of nivolumab therapy regardless of the PD-L1 expression level,2 while the efficacy of nivolumab therapy for a non-squamous histology was predicted to depend on the PD-L1 expression level.1 Some studies have suggested possible predictors, such as the nonsynonymous mutation burden,6 and the presence of CD8+ tumor-infiltrating lymphocytes.7 However, these biomarkers are not entirely reliable, and their investigation is labor-intensive and impractical for daily clinical practice.
The CYFRA 21-1 level reflects an increasing tendency toward differentiation into SCC.5 Lung SCCs have a higher mutation burden than lung adenocarcinomas.8 Therefore, we hypothesized that a high serum CYFRA 21-1 level is correlated with a greater efficacy of nivolumab therapy in lung adenocarcinoma patients. In this study, we investigated the predictive implications of the CYFRA 21-1 level in advanced lung adenocarcinoma patients treated with nivolumab therapy.
Materials and methods
Study design
We retrospectively reviewed data from 79 advanced lung adenocarcinoma patients treated with nivolumab at the Shizuoka Cancer Center between December 2015 and September 2016.
Patients
The inclusion criteria were as follows: histologically confirmed adenocarcinoma; diagnosis of stage IV including postoperative recurrence; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2; treated with at least one previous chemotherapy regimen; and adequate organ functions. The pathological diagnoses were performed according to the World Health Organization (WHO) classification criteria.9 The study was conducted with...