Predictive clinical parameters for the response of nivolumab in pretreated advanced non-small-cell lung cancer

Abstract

BackgroundNivolumab offers a superior survival benefit over docetaxel in patients with advanced, previously treated non-small-cell lung cancer (NSCLC). An association between programmed cell death ligand-1 (PD-L1) expression and the efficacy of nivolumab has been reported in many studies. However, the association between the clinical parameters and efficacy of nivolumab remains unclear in advanced NSCLC patients.ResultsAmong 124 patients, 108 (88%) were performance status (PS) 0 to 1. PD-L1 expression was assessed in 89 patients, with 51 (57%) patients having PD-L1 positive expression. In all patients, the objective response rate (ORR) in patients with elevated CRP levels (≥ 1 mg/dl) was significantly worse than those without elevated CRP levels (< 1 mg/dl) (8.3 vs 23.4%, p = 0.0180). The PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) were significantly associated with a shorter PFS and OS in patients treated with nivolumab. Multivariate analyses showed that the PS (≥ 2), smoking index (< 400), CRP levels (≥ 1 mg/dl) and LDH (≥ 245 IU/L) and PD-L1 expression were significant factors associated with a longer PFS of nivolumab.Materials and MethodsWe retrospectively analyzed 124 patients who received nivolumab as a subsequent treatment. The patient characteristics, laboratory data at baseline (C-reactive protein [CRP] and lactate dehydrogenase [LDH]), PD-L1 expression, nivolumab response, progression-free survival (PFS), and overall survival (OS) were evaluated.ConclusionsClinical parameters, such as PS, serum CRP, serum LDH, and smoking status, were significantly associated with the response duration and survival in patients treated with nivolumab.

The prognostic values of CRP kinetics and initial apoA-I in patients with advanced NSCLC: a retrospective study

“…As we all known, CRP is a strong prognostic predictor in many cancers. As reported previously 14,33 , patients without elevation of pretreatment CRP level have better prognosis than those with elevated pretreatment CRP level. Wilop et al found that normalization of CRP during chemotherapy was associated with better prognosis 15 .…”

“…It's also found that a high circulating CRP level in lung cancer patients also indicated shorter survival 12,13 . A study on advanced cancer patients revealed that baseline CRP was an independent prognostic factor for survival in patients with advanced NSCLC receiving palliative rst-line chemotherapy 14 . Another available evidence shows that measurement of CRP both before initiation and during a platinum-based chemotherapy may provide prognostic information for the individual patient with advanced NSCLC.…”

Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer with ALK Rearrangement

“…There are several reports, including our report, that ICI treatment has less efficacy in patients with poor PS or high CRP. It is thought that these are due to immunosuppression and the relationship with inflammatory cytokines [31][32][33], but the reasons are not clear. Therefore, CRP is not a clear biomarker.…”

Lactate dehydrogenase: a marker of diminished antitumor immunity

“…However, retrospective data support a relationship between LDH levels and clinical outcome following immunotherapy in other tumor types (Table 1). [6][7][8][9][10][11] In this review, we describe mechanisms that may result in elevated LDH levels in cancer patients. Elevated LDH levels are the product of enhanced glycolytic activity of the tumor and tumor necrosis due to hypoxia, the latter being associated with high tumor burden.…”