Immunotherapy in patients with early stage resectable nonsmall cell lung cancer

Purpose of review ‘Early-stage’ nonsmall cell lung cancer (NSCLC) refers to stage I and stage II disease, and selected cases of stage IIIA disease where complete tumor resection is feasible. Surgery is the standard treatment for early NSCLC, but the overall 5-year survival remains below 50%. The addition of adjuvant cisplatin-based chemotherapy to surgery improved 5-year survival rates by 5–10%, but no significant therapeutic innovation has been established thereafter. We review recent and ongoing studies looking how immunotherapy may improve the outcome of these patients. Recent findings Antigen-specific immunotherapy (cancer vaccination) did not fulfill its promise in a large phase III randomized trial in completely resected early-stage NSCLC. Over the past few years, immunotherapy with immune checkpoint inhibition (ICI) has led to remarkable progress in nononcogene addicted metastatic NSCLC. We review ongoing clinical investigations that want to translate these benefits to earlier stages of NSCLC. Both adjuvant and neoadjuvant large randomized controlled trials with ICI are ongoing. Summary Although from a mechanistic perspective the neoadjuvant administration may be preferred, it is crucial that both adjuvant and neoadjuvant trials are recruited as planned, to have a balanced view how ICI therapy may ultimately improve cure rates in these patients.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research

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Abstract Mutations in KEAP1 and NFE2L2 (encoding the protein Nrf2) are prevalent in both adenocarcinoma and squamous subtypes of non-small cell lung cancer. The consequence of these mutations is stabilized Nrf2 and chronic induction of several Nrf2 target genes. Here, downregulation of Nrf2 resulted in modest growth inhibition of cells growing in 2D; this was more pronounced in cell lines expressing mutant KEAP1. In contrast, downregulation of Nrf2 caused almost complete regression of established KEAP1-mutant tumors in mice, with little effect on wildtype (WT) KEAP1 tumors. The strong dependency on Nrf2 could be r...
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Tags: Cancer Res Source Type: research
Conclusion.NLR and PLR may predict the appearance of irAEs in non‐oncogene‐addicted aNSCLC, although this conclusion warrants prospective validation.Implications for Practice.This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune‐related adverse events (irAEs) in patients with advanced non‐small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Lung Cancer Source Type: research
Abstract ALK and ROS1 kinases have become promising therapeutic targets since Crizotinib was used to treat non-small-cell lung cancer clinically. Aiming to explore new potent inhibitors, a series of 2-amino-4-(1-piperidine) pyridine derivatives that stabilized a novel DFG-shifted conformation in the kinase domain of ALK were designed and synthesized on the base of lead compound A. Biological evaluation highlighted that most of these new compounds could also potently inhibit ROS1 kinase, leading to the promising inhibitors against both ROS1 and ALK. Among them, the representative compound 2e stood out potent anti-p...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
Authors: Tagliamento M, Genova C, Rossi G, Coco S, Rijavec E, Dal Bello MG, Boccardo S, Grossi F, Alama A Abstract Introduction: The management of non-small cell lung cancer (NSCLC) has been substantially improved in the last few years; it has been revolutionized by a patient-tailored approach, especially in the oncogene addicted disease, and by novel combinations containing immune checkpoint inhibitors. However, chemotherapy still represents a mainstay that persists over the decades with limited novelties. Tubulin inhibitors belong to different sub-classes of drugs that share the capability to interfere with mitos...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
Opinion statementTargeted therapies and more recently immune checkpoint inhibitors (ICI) have transformed the treatment landscape of advanced NSCLC. Clinical trials investigating immune checkpoint inhibitors (ICI) have usually excluded patients with oncogenic drivers, so that the outcome of these agents in this population is poorly known. In patients with oncogenic addiction, targeted therapy remains clearly the best option, and the place of immunotherapy in this population has not been clearly defined yet.Based on available data, we suggest that (i) immunotherapy single agent should be proposed only after exhaustion of mo...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Abstract While the prognosis of metastatic non-small-cell lung cancer has shown significant progress these last years, notably with the discovery of oncogen-driven subtypes and the development of targeted therapies, significant improvements are still needed. More recently, numerous authors studied the oligo-metastasis concept, where the metastasis are limited in number and sites involved, and that could benefit from an aggressive approach of these lesions, for instance with the help of stereotactic radiotherapy. Nevertheless, there is no clear consensus existing for the time being for the treatment of these tumors...
Source: Cancer Radiotherapie - Category: Cancer & Oncology Authors: Tags: Cancer Radiother Source Type: research
Authors: Gustin P, Botticella A, Tselikas L, Mercier O, Le Péchoux C, Levy A Abstract Lung cancer is the leading cause of cancer-related mortality and more than half of the cases are diagnosed at a metastatic stage. Major progress in terms of systemic treatments has been achieved in recent decades. Access to new anti-PD-(L) 1 immunotherapies and targeted therapies for non-small cell lung cancer (NSCLC) with oncogenic addiction such as EGFR mutation or ALK rearrangement have led to improved outcomes. Patients with limited progression of their disease during systemic treatment may be a particular subgroup. Thi...
Source: Revue des Maladies Respiratoires - Category: Respiratory Medicine Tags: Rev Mal Respir Source Type: research
CONCLUSION: NLR and PLR may predict the appearance of irAEs in non-oncogene-addicted aNSCLC, although this conclusion warrants prospective validation. IMPLICATIONS FOR PRACTICE: This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for an easy ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Liu G Abstract BACKGROUND: In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health-related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses. MATERIALS AND METHODS: In a prospective observational cohort study (2014-2016), outpatients with stage IV lung cancer completed demographic and EQ-5D-3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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