Treatment of ALK-positive nonsmall cell lung cancer: recent advances

Purpose of review The review will highlight recent advances in development of ALK-TKIs and management of patients with ALK-positive nonsmall cell lung cancer. Recent findings There has been rapid progress in the use of targeted therapies for ALK-positive NSCLC. Since the discovery, development and approval of crizotinib in 2011, three second-generation ALK-TKIs, ceritinib, alectinib and brigatinib have been approved by the FDA. A range of newer generation ALK inhibitors with improved potency against ALK and against mutations that confer resistance to crizotinib are in clinical development. Summary Our review will discuss the recent phase III data with ceritinib and alectinib as well as clinical trials with other ALK inhibitors. We will also address two important issues in the management of ALK-positive NSCLC, prevention and treatment of brain metastases and management of emergent ALK-TKI resistance mechanisms.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research

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Conclusions: Current trial eligibility criteria are often strict and limit the enrolment of patients in clinical trials. Our results suggest that, depending on the chosen drug, its toxicities and tolerability, eligibility criteria could be carefully reviewed and relaxed. PMID: 30111974 [PubMed - in process]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
We report here the first patient with co-existing ROS1 fusion and de-novo MET amplification to receive crizotinib in China. Treatment of our patient was effective with targeted therapy based on a precise diagnosis. Advanced or metastatic NSCLC patients with co-existing ROS1 fusion and de-novo MET amplification are sensitive to crizotinib. These uncommon driver gene mutations may be missed using the current first-generation detection assay. We must be aware of the incidence of concomitant ROS1 fusion and de-novo MET amplification because NSCLC patients could benefit from targeted therapy. PMID: 30095326 [PubMed - as supplied by publisher]
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Authors: Attili I, Karachaliou N, Conte P, Bonanno L, Rosell R Abstract INTRODUCTION: Epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) is a subset of lung cancer with demonstrated response to targeted therapies. However, resistance to the first targeted approach usually occurs within the first year, and it is associated in 50-60% of cases to the T790M resistance mutation. Areas covered: The review provides an overview on the significance of the presence of the T790M mutation, its detection, treatment options and subsequent mechanisms of resistance. Expert commentary: Osim...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Conclusion: The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors. PMID: 30064202 [PubMed - as supplied by publisher]
Source: Journal of Korean Neurosurgical Society - Category: Neurosurgery Tags: J Korean Neurosurg Soc Source Type: research
AbstractBackgroundTo assess the impact of location versus number of extra-pulmonary metastatic sites (EPMS) on survival in stage IV non-small cell lung cancer (NSCLC).Methods and materialsRetrospective analysis was conducted on patients diagnosed during 1999 –2013 with stage IV, M1b (AJCC 7th edition) NSCLC using the large, institutional Glans-Look Database, which contains patient demographic, clinical, pathological, treatment, and outcome information. We assessed the impact of location and number of EPMS and identified correlates of overall survival using the Kaplan–Meier method and Cox regression.ResultsWe id...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Central nervous system metastasis in non-small cell lung cancer remains a therapeutic challenge and confers a poor prognosis. Here we describe a patient with lung adenocarcinoma, parenchymal brain metastases, and leptomeningeal carcinomatosis who demonstrated a sustained response to programmed death 1 inhibition combined with stereotactic radiosurgery. PMID: 30072392 [PubMed - as supplied by publisher]
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Background: The present study aims to assess the therapeutic effect of whole brain radiotherapy (WBRT) for brain metastases from non-small cell lung cancer stratified by graded prognostic assessment (GPA) through meta-analysis. Methods: The Cochrane Library, PubMed, Ovid (Elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P 
Source: Medicine - Category: Internal Medicine Tags: Research Article: Systematic Review and Meta-analysis Source Type: research
SummaryThe administration of target inhibitors is paramount to grant the longest survival in patients with ALK-positive non-small cell lung cancer (NSCLC). The eventual resistance to tyrosine kinase inhibitors (TKI) is monitored clinically and radiologically for prompt molecule shift to further generation TKI, if available. However, the early radiological detection of progression pattern (e.g. nodule onset) should be regarded with caution because overlaps exist with non-tumor cell proliferation and/or accumulation. Here we report the case of a stage IVALK-rearranged NSCLC patient exposed to serial crizotinib, brigatinib, c...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
Authors: Ashour Badawy, Khedr, Omar A, Bae S, Arafat W, Grant S Abstract Background: Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception of targeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastases and this may explain, in part, the wide range of responses to same lines of therapy. Aim of work: In this work we tried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lung cancer patients who received different treatments line. Methods: A retrospecti...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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