Clinical and Hematologic Parameters Address the Outcomes of Non-Small-Cell Lung Cancer Patients Treated With Nivolumab

Facchinetti, Francesco; Veneziani, Michele; Buti, Sebastiano; Gelsomino, Francesco; Squadrilli, Anna; Bordi, Paola; Bersanelli, Melissa; Cosenza, Agnese; Ferri, Leonarda; Rapacchi, Elena; Mazzaschi, Giulia; Leonardi, Francesco; Quaini, Federico; Ardizzoni, Andrea; Missale, Gabriele

doi:10.2217/imt-2017-0175

Cited by 34 publications

(16 citation statements)

References 34 publications

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“…Neutrophil-to-lymphocyte ratio (NLR) is a marker of chronic inflammation and reflects the alterations in the peripheral blood leukocytes associated with inflammation. This marker has been extensively associated with poor outcomes in NSCLC and other solid tumors in the pre- with different cutoff values [10,13,14,21]. Moreover, some studies have reported a potential predictive role for changes of NLR levels during treatment with nivolumab [12,22,23], suggesting that treatment with anti-PD-1/PD-L1 agents may be associated with a broad spectrum of changes in the immune microenvironment of the tumor, leading to decrease in the neutrophil count and increase in the lymphocyte count in responding patients.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

et al. 2020

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Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab. Methods: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging.

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Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

et al. 2020

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“…Survival data were analyzed using a Cox proportional hazard regression model adjusted for established clinical and biological risk factors. Following biological and clinical parameters were studied as prognostic factors: nivolumab plasma C min at day 14 (<median value), nivolumab plasma C min at day 28 (<median value), ECOG performance status [37,38], number of metastasis [38,39], neutrophil-to-lymphocyte ratio (NLR) (<median value) [39,40], and baseline use of corticosteroids and tumor PD-L1 protein expression (>median value) [14,41]. A Spearman’s rank test was used to investigate the relationship between nivolumab plasma C min and grade >2 irAE.…”

Section: Methodsmentioning

confidence: 99%

Is there an Exposure–Response Relationship for Nivolumab in Real-World NSCLC Patients?

Bellesœur

Ollier

Allard

et al. 2019

Cancers

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Pharmacokinetic/pharmacodynamic data from real-world cohort are sparse in non small–cell lung cancer (NSCLC) patients treated with nivolumab. The aim of this prospective observational study was to explore the exposure-response relationship for effectiveness and toxicity of nivolumab in 81 outpatients with metastatic lung cancer. Nivolumab plasma trough concentrations (Cmin) were assayed at days 14, 28, and 42. Prognostic factors (including Cmin) regarding progression-free survival (PFS) and overall survival (OS) were explored using a multivariate Cox model. A Spearman’s rank test was used to investigate the relationship between Cmin and grade >2 immune-related adverse events (irAE). Mean nivolumab Cmin was 16.2 ± 6.0 µg/mL (n = 76), 25.6 ± 10.2 µg/mL (n = 64) and 33.4 ± 11.3 µg/mL (n = 53) at days 14, 28, and 42, respectively. No pharmacokinetic/pharmacodynamic (PK/PD) relationship was observed with either survival or onset of irAE. Multivariable Cox regression analysis identified Eastern Cooperative Oncology Group Performance Status (hazard ratio 1.85, 95%confidence interval 1.02–3.38, p-value = 0.043) and baseline use of corticosteroids (HR 8.08, 95%CI 1.78–36.62, p-value = 0.007) as independent risk factor for PFS and only baseline use of corticosteroids (HR 6.29, 95%CI 1.46–27.08, p-value = 0.013) for OS. No PK/PD relationship for nivolumab was observed in real-world NSCLC patients. This supports the recent use of flat dose regimens without plasma drug monitoring.

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“…Furthermore, the response to first-line chemotherapy before nivolumab had also been described previously for melanoma [15] and NSCLC [7,16–18]. Those responses could be caused by antigens released after tumor-cell death that would stimulate the immune T-cell response and enhance the immunotherapy mechanism of action [19–21].…”

Section: Discussionmentioning

confidence: 75%

Neutrophil-to-lymphocyte ratio evolution is an independent predictor of early progression of second-line nivolumab-treated patients with advanced non-small-cell lung cancers

et al. 2019

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Introduction Although second-line immunotherapy obtained better outcomes than chemotherapy for patients with advanced non-small–cell lung cancers (NSCLCs), it is expensive and only a minority of patients seem to benefit, based on early tumor progression post-immunotherapy. Notable host inflammation, characterized by biomarkers (e.g. neutrophil-to-lymphocyte ratio (NLR])), prolongs overall survival (OS) of surgery-, chemotherapy- and immunotherapy-treated patients. To our knowledge, no previous studies used biomarker evolution to analyze the immunotherapy impact on host inflammation. Immunotherapy mainly exerts its activity by lymphocyte reactivation. Methods This retrospective study was conducted on patients, selected by their progression status just before their 4 th nivolumab injection, and treated at Bordeaux and Limoges University Hospitals. A comparative group of at least 1-year responders was also selected. Clinical parameters and hematological data just before the 1 st (baseline) and 4 th nivolumab infusions were collected to calculate the NLR change (ΔNLR) between those two infusions. The combined impact of the different known prognostic factors was also analyzed with multivariable analyses. Results Fifty-nine patients were included. The 29 early progressors had significantly more frequent ΔNLR > 1 ( p = 0.0007), OR 18.08 [95% CI 2.96–246.24] with progressive disease as best response to prior treatment line ( p = 0.0014). ΔNLR < 1 prolonged OS (HR 0.001 [0.0007–0.18], p = 0.001); as did a partial response to prior line of systemic treatment (HR 0.14 [0.03––0.56], p = 0.005). Conclusion Based on selected early progressors given second-line immunotherapy for advanced NSCLC, progression as best response to prior treatment and ΔNLR > 1 characterized the early progressors and shortened OS after starting nivolumab. This phenomenon questions nivolumab utility in patients with a major host neutrophil inflammation.

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Clinical and Hematologic Parameters Address the Outcomes of Non-Small-Cell Lung Cancer Patients Treated With Nivolumab

Abstract: Nivolumab efficacy in non-small-cell lung cancer patients is influenced by clinicopathological parameters and specific leucocyte subsets.

Cited by 34 publications

References 34 publications

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

Is there an Exposure–Response Relationship for Nivolumab in Real-World NSCLC Patients?

Neutrophil-to-lymphocyte ratio evolution is an independent predictor of early progression of second-line nivolumab-treated patients with advanced non-small-cell lung cancers

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