Therapeutic strategies in advanced ALK positive non-small cell lung cancer.

The objective of this paper is to synthesise current knowledge on ALK rearrangement and its impact on the management of advanced NSCLC. Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy. Unfortunately, the emergence of drug resistance leads to tumor progression. In patients with oligoprogressive disease if local ablative therapy can be effected, continuing with the same ALK tyrosine kinase inhibitor is one option. In patients with progression, clinicians may consider switching to another therapy. Rebiopsy of the tumor or liquid biopsy could be attempted to identify the mechanisms of resistance and to customize ALK-target therapy. The emergence of crizotinib drug resistance has prompted the development of next generation drugs including ceritinb, alectinib, brigatinib and lorlatinib. The ability to quickly develop targeted therapies against specific oncogenic drivers will require close co-operation between pathologists, pulmonologists and oncologists in the future to keep pace with drug discoveries and to define optimal therapeutic strategies. PMID: 31727555 [PubMed - as supplied by publisher]
Source: Revue des Maladies Respiratoires - Category: Respiratory Medicine Tags: Rev Mal Respir Source Type: research

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Shekar Patil, Krishna Kumar RathnumIndian Journal of Cancer 2019 56(5):1-9 In leptomeningeal metastasis (LM), malignant lung cancer cells reach the sanctuary site of the leptomeningeal space through haematogenous or lymphatic route and thrive in the leptomeninges because of restricted access of chemotherapeutic agents across the blood brain barrier. The incidence of LM is 3%–5% in non-small cell lung cancer (NSCLC) patients; the incidence is higher in patients with anaplastic lymphoma kinase (ALK) gene rearrangement or epidermal growth factor receptor (EGFR) mutations. However, the real-world burden of undia...
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
We examined publication bias and excess significance bias. 63 articles corresponding to 247 meta-analyses were eligible. Nine meta-analyses were classified to have convincing evidence, and 75 were classified as suggestive evidence. The clinical benefit of immunotherapy was supported by convincing evidence in the following settings: anti-PD-1/PD-L1 monoclonal antibody (mAb) therapy for treating advanced melanoma and non-small cell lung cancer (NSCLC), the combination of rituximab and chemotherapy for treating chronic lymphocytic leukemia and B-cell non-Hodgkin’s lymphoma, adoptive cell immunotherapy for NSCLC, and...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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
The discovery of kinase gene rearrangements as oncogenic drivers in non-small cell lung carcinomas (NSCLCs), and the subsequent development of targeted therapies (TTs) have dramatically changed the landscape of this small subset of malignancies. Development of potent tyrosine-kinase inhibitors (TKIs) targeting fusions involving the genes ROS1, anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine receptor kinase (NTRK) have provided overall response rates (ORRs) as high as 70-80% in metastatic disease, overcoming chemotherapy regimens as first-line treatment in this setting [1].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
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 firs...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports 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
ConclusionCeritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front ‐line treatment of ALK‐positive advanced NSCLCs.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
In 2007, the first anaplastic lymphoma kinase (ALK) fusion was described in non-small cell lung cancer (NSCLC)[1]. In 2013, a phase 3 study demonstrated a significant improvement in progression free survival (PFS) and overall survival (OS) in patients with metastasized ALK positive lung cancer treated with crizotinib compared to chemotherapy[2]. Subsequently, testing for ALK aberrations in patients with metastasized adenocarcinoma of the lung was recommended by international guidelines [3,4].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
ConclusionAs a first-line treatment for advanced NSCLC with rearrangement of anaplastic lymphoma kinase, ceritinib is unlikely to be cost-effective at the current price from the Chinese healthcare perspective. To meet the treatment demands of patients, it may be a better option to reduce the price or provide appropriate drug assistance policies.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
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