Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds.

Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds. Expert Opin Investig Drugs. 2019 Jun 04;: 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 mitosis by a direct action on the microtubule system. Among them, taxanes and vinca alkaloids still have a prominent role in clinical practice. Areas covered: This review summarizes the mechanisms of action, current role and future directions of microtubule targeting agents; we focus on investigational agents in phase I and II clinical trials. Expert opinion: Chemotherapy maintains a pivotal role in the treatment of NSCLC. New generation agents that have the potential to overcome the mechanisms of resistance to the available drugs may provide new therapeutic opportunities. Predictive biomarkers derived from combination strategies and phase III studies are necessary...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

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Authors: Rossi A Abstract Introduction: Nonsquamous non-small-cell lung cancer (NSCLC) is divided in oncogene-addicted subgroups, highly expressed programmed death ligand-1 (PD-L1 ≥ 50%) subgroup, and "negative" subgroup. The latter represents the most common group comprising about 50% of all new diagnoses of nonsquamous NSCLC. For this group, chemotherapy was the standard approach with pemetrexed- and/or bevacizumab-based regimens reaching an overall survival of about 12-17 months. Areas covered: This review will focus on the new options for combination therapies, which have already recently arrived o...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med 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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