Angiogenesis inhibition in non-small cell lung cancer: a critical appraisal, basic concepts and updates from American Society for Clinical Oncology 2019

Purpose of review Recently, the combination of antiangiogenic agents, chemotherapy and immunotherapy has shown synergistic anticancer effects in non-small cell lung cancer (NSCLC). The future for this approach appears bright in lung cancer treatment; however, many challenges remain to be overcome regarding its true potential, optimal sequence and timing of therapy, and safety profile. In this review, we will discuss the current status and future direction of antiangiogenic therapy for the treatment of NSCLC, and highlight emerging strategies, such as tumor vessel normalization (TVN). Recent findings Bevacizumab was the first antiangiogenic agent approved for the treatment of advanced NSCLC. Recently, the combination of chemotherapy/antiangiogenic therapy with immunotherapy showed high efficacy in first-line settings. A subgroup of patients with liver metastasis and driver mutation-addicted tumors benefited most, suggesting that the metastatic location, as well as the genetic background of the tumor, are key determinants for therapy responses. Summary The efficacy of antiangiogenic therapies in unselected patients is rather limited. The tumor microenvironment has appeared to be more complex and heterogeneous than previously assumed. Only a contextual rather than a cell-specific approach might provide valuable insights towards the clinical validation of combinational therapies.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research

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AbstractBackgroundNon-small cell lung cancer (NSCLC) is one of the commonest disease worldwide and the leading cause of cancer-related death. Incidence increases with age and reaches a peak in senility, when patients ’ (pts) comorbidities may limit the efficacy of treatments. At this time, no homogeneous indications are available for elderly NSCLC pts and the optimization of treatment, with the lowest side effects, is still an unmet need, also after the introduction of innovative drugs. The ribonucleotide redu ctase catalytic subunit M1(RRM1), the DNA-excision repair protein ERCC1 and the thymidylate synthetase (TS) ...
Source: Annals of Oncology - Category: Cancer & Oncology 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
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
AbstractImmune checkpoint inhibition (ICI) immunotherapy has revolutionized the approach to metastatic non-small-cell lung cancer (NSCLC). In particular, antibodies blocking the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand (PD-L1) are associated with higher response rates, improved overall survival and better tolerability as compared with conventional cytotoxic chemotherapy. Recently, ICI has moved from the second-line to the first-line setting for many patients with non-oncogene-addicted NSCLC, either alone or in combination with chemotherapy. The next logical step is to examine this therapy in p...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with theKRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.
Source: Annals of Oncology - Category: Cancer & Oncology 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
AbstractEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation...
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Abstract The era of personalized medicine for advanced-stage non-small-cell lung cancer (NSCLC) began when biomarker-based evidence of molecular pathway and/or oncogene addiction of the tumour became mandatory for the allocation of specific targeted therapies. More recently, the immunotherapy revolution, specifically, the development of immune-checkpoint inhibitors (ICIs), has dramatically altered the NSCLC treatment landscape. Herein, we compare and contrast the clinical development of immunotherapy and oncogene-directed therapy for NSCLC, focusing on the role of predictive biomarkers. Immunotherapy biomarkers ar...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Nat Rev Clin Oncol Source Type: research
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-spe...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research
CONCLUSION: The present paper discusses the old and new treatment opportunities, proposing a shared algorithm for second-line setting in advanced NSCLC. PMID: 29992894 [PubMed - as supplied by publisher]
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Curr Clin Pharmacol Source Type: research
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