Abstract

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58–6.60, P = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 109/L versus low: ≤ 0.93 × 109/L, HR: 0.38, 95%CI: 0.23–0.62, P < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15–4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01–17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56–1.45, P = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41–1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.

Highlights

  • Non-small cell lung cancer (NSCLC) represents the leading cause of cancer-mortality in the United States and in Europe [1,2]

  • Data were extracted from medical records including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, histologic subtype, smoking history, epidermal growth factor receptor (EGFR) mutation status, anaplastic lymphoma kinase (ALK) translocation status, central nervous systems (CNS) involvement, programmed cell death ligand 1 (PD-L1) expression on tumor cells, immune-checkpoint inhibitor therapy line, immune-checkpoint inhibitor substance, prior or concomitant denosumab application, prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy, antibiotic treatment status, subsequent therapy protocols, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and prior radiotherapy to the primary tumor or metastases

  • The results of our analysis demonstrate the practicality of estimating overall survival (OS) from initiating the PD-1/PD-L1 blockade based on baseline ALC and ECOG performance status in advanced NSCLC (aNSCLC)

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Summary

Introduction

Non-small cell lung cancer (NSCLC) represents the leading cause of cancer-mortality in the United States and in Europe [1,2]. Despite achievement of overall response rates (ORR) between 45% to 48% by immune-checkpoint blockade (ICB) as monotherapy in programmed cell death ligand 1 (PD-L1) high expressing tumors or in combination with chemotherapy and despite a plateauing of overall survival (OS) curves after 12 to 15 months, half of the patients experience disease progression after 8.8 to 10.3 months from initiation of first-line therapy and will necessitate further systemic treatment [8,9]. Due to the rising costs caused by the therapeutic approach of ICB and, in order to select patients that will derive clinical benefit from currently approved immune-checkpoint inhibitor protocols, the identification of available predictive baseline parameters is an absolute necessity in the daily clinical practice. Several attempts have been made to predict the therapy response or treatment failure to ICB based on patient and tumor characteristics

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