Intracranial remission with brigatinib rechallenge as fifth-line ALK inhibition therapy in a lung cancer patient

Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors have been developed for the treatment of EML4-ALK-rearranged non-small-cell lung cancer, with the newer generation agents brigatinib, alectinib and lorlatinib showing pronounced central nervous system activities. Intracranial efficacy is an important feature for these agents, as metastatic lesions frequently occur in the central nervous system in the ALK-positive setting. Here, we report on an updated case of a patient who received her diagnosis in 2005 and has had disease progression with new lesions on six occasions over the last 8 years. During the first two progressions, only local recurrence was observed. After that, the lungs stayed clear and the patient progressed exclusively in the brain and spinal cord. Initial treatments consisted of chemotherapy and radiotherapy. In 2012, ALK-directed targeted therapy became available, and crizotinib was administered. The treatment was switched to brigatinib 3 years later because of spinal cord lesions. Brigatinib induced partial remission and was followed by lorlatinib and, later on, alectinib, when new metastases arose in the spinal cord and brain. Each of these drugs promoted complete remission of the recent lesions. In November 2018, imaging showed multiple cerebral metastases. As radiotherapy was not an option because of previous irradiation, and as chemotherapy cannot be expected to be active in the brain, the patient underwent brigatinib rechallenge, which l...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research

Related Links:

Conclusions: This retrospective analysis of a real-world experience confirms the therapeutic benefit of crizotinib in advanced ALK-positive NSCLC. Our data showed crizotinib is tolerable and effective, comparable with literature report. Occasional serious cardiac toxicity requires attention. PMID: 31656659 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
We describe here a case of 48 y.o. male patient with ALK-positive NSCLC who was clinically managed for 6.5 years from the diagnosis. The tumor was surgically resected, but 8 months later multiple brain metastases were discovered. The patient started receiving platinum-based chemotherapy and then was enrolled in a clinical trial of second-generation ALK inhibitor ceritinib, which resulted in a 21 months stabilization. Following disease relapse, the patient was successfully managed for 33 months with different lines of chemo- and local ablative therapies. Chemotherapy regimens, including off-label combination of crizotinib +...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfo...
Source: Cancer Radiotherapie - Category: Cancer & Oncology Authors: Tags: Cancer Radiother Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Lung cancer is the most common tumor and the leading cause of cancer-related death worldwide. Approximately 6.7% of non-small-cell lung cancers (NSCLCs) show anaplastic lymphoma kinase (ALK) rearrangement and could benefit from ALK-targeted treatment. Various anti-ALK drugs have been developed during the past years, but it is actually controversial which sequence and which ALK inhibitor is recommended for a single patient. Leptomeningeal carcinomatosis (LC) is associated with a poor prognosis, with an overall survival of 2–4 months for treated patients. The data about LC management derive mainly from retrospective st...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: CASE REPORTS Source Type: research
Authors: Melosky B, Cheema P, Agulnik J, Albadine R, Bebb DG, Blais N, Burkes R, Butts C, Card PB, Chan AMY, Hirsh V, Ionescu DN, Juergens R, Morzycki W, Poonja Z, Sangha R, Tehfe M, Tsao MS, Vincent M, Xu Z, Liu G Abstract Background: Inhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Griesinger F, Roeper J, Pöttgen C, Willborn KC, Eberhardt WEE Abstract The progress in molecular biology has revolutionized systemic treatment of advanced non-small-cell lung cancer (NSCLC) from conventional chemotherapy to a treatment stratified by histology and genetic aberrations. Tumors harboring a translocation of the anaplastic-lymphoma-kinase (ALK) gene constitute a distinct genetic and clinico-pathologic NSCLC subtype with patients with ALK-positive disease being at a higher risk for developing brain metastases. Due to the introduction of effective targeted therapy with ALK-inhibitors, today, ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionsYoung patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
This article is protected by copyright. All rights reserved.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Conclusion: In this initial study, 18F-FLT radiotracer uptake correlated well with clinical outcome of the patients, successfully differentiating proliferative malignant lesions from other benign concomitant etiologies. Scan results demonstrated low grade to absent FLT tracer uptake in benign inflammatory/infective cells as compared to higher grade concentration in tumor cells.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Oncology Posters Source Type: research
More News: Brain | Brain Cancers | Cancer | Cancer & Oncology | Chemotherapy | Lung Cancer | Lymphoma | Neurology | Non-Small Cell Lung Cancer