Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations.

08:00 EDT 12th April 2019 | BioPortfolio

Summary of "Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations."

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.


Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0215292


DeepDyve research library

PubMed Articles [51121 Associated PubMed Articles listed on BioPortfolio]

Pseudoprogression in previously treated patients with non-small cell lung cancer who received nivolumab monotherapy: A multicenter retrospective cohort study.

Nivolumab is effective in the treatment of previously treated patients with advanced non-small cell lung cancer (NSCLC). However, its radiological evaluation is challenging because of atypical pattern...

Hyperprogressive disease in patients with non-small cell lung cancer treated with nivolumab: A case series.

Nivolumab is an anti-PD-1 blocking monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). However, some patients on immunotherapy may experience rapid progression and wo...

Correlation between nivolumab exposure and treatment outcomes in non-small-cell lung cancer.

Nivolumab treatment is subject to large interpatient variability in both efficacy and toxicity, which may partly be explained by differences in nivolumab exposure. Exposure-response relationships in r...

Change in the lymphocyte-to-monocyte ratio is an early surrogate marker of the efficacy of nivolumab monotherapy in advanced non-small-cell lung cancer.

Nivolumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, has been shown to yield a durable response and significant prolongation of the survival in some patients with non-small-c...

Peripheral T cell cytotoxicity predicts T cell function in the tumor microenvironment.

Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of canc...

Clinical Trials [12163 Associated Clinical Trials listed on BioPortfolio]

A Study for Identification of Predictive Immune Biomarker in Peripheral Blood for Nivolumab Therapy in NSCLC Patients

The study aimed to elucidate predictive immune related biomarker to the responsiveness to the PD-1 blockade and evaluate the dynamics of immune cells in peripheral blood from NSCLC patient...

18F-PD-L1 PET/CT in Nivolumab Treated Patients With NSCLC

A multicenter single arm biomarker exploration and validation study. Eighty patients with NSCLC that are eligible for nivolumab treatment according to EMA label and national guidelines wil...

BIOLUMA: Biomarkers for Nivolumab and Ipilimumab and Evaluation of the Combination in Lung Cancer

BIOLUMA is a multicentric non-randomised phase II trial in patients with non-squamous non-small cell lung cancer (NSCLC) (Cohort 1) and patients with small-cell lung cancer (SCLC) (Cohort ...

A Trial of CV301 in Combination With Nivolumab Versus Nivolumab in Subjects With Previously Treated Non-Small Cell Lung Cancer

The objective of the proposed clinical study is to investigate the safety and tolerability of CV301 in combination with OPDIVO® (nivolumab), an anti PD1- inhibitor, compared to nivolumab ...

Docetaxel Plus Nivolumab or Docetaxel Alone in Patients With Advanced Non-squamous NSCLC Previously Treated With Nivolumab

This is a randomized phase II study assessing the activity of docetaxel combined with nivolumab compared to docetaxel alone in metastatic or recurrent non-squamous non-small cell lung canc...

Medical and Biotech [MESH] Definitions

Analysis of the level of specific BIOMARKERS in a pregnant woman's sera to identify those at risk for PREGNANCY COMPLICATIONS or BIRTH DEFECTS.

A factor associated with the well-being of living organisms that is used as a measure of environmental change and or influence. For example, aldehyde dehydrogenase expression in earthworm tissue is used as an indication of heavy metal pollution in soils. Distinguish from BIOMARKERS.

Meta-analysis of randomized trials in which estimates of comparative treatment effects are visualized and interpreted from a network of interventions that may or may not have been evaluated directly against each other. Common considerations in network meta-analysis include conceptual and statistical heterogeneity and incoherence.

Strategy for the analysis of RANDOMIZED CONTROLLED TRIALS AS TOPIC that compares patients in the groups to which they were originally randomly assigned.

An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.

Quick Search


DeepDyve research library

Relevant Topics

Gilotrif (afatinib)
GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Searches Linking to this Article