Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study

We describe outcomes of real-life patients according to the treatment strategy received.PatientsWe retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions.ResultsAfter a median follow-up of 26  months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9–11.2] and 11.1 months [CI 95% 9.2–13.8], respectively, while TTF were 10.2 [CI 95% 8.5–12.6] and 11.9 months [CI 95% 9.7–17.4], respectively, being consistent across the different settings. The composed outcomes ( the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3–33.7] in PFS and 30.4 months [CI 95% 24.7–34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8–54.5]. Patients receiving crizo tinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0–73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6–NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3–34.0)] (P 
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research

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This study evaluated the distribution of the crizotinib patient information brochure (PIB) in Europe and patient knowledge of the key messages in the PIB. A cross‐sectional survey was conducted in 10 European countries among pa tients who received crizotinib to ascertain whether each patient received and read the PIB, and his/her knowledge of its key messages on hepatotoxicity, interstitial lung disease/pneumonitis, QTc prolongation, bradycardia, and vision disorders. Of the 341 patients contacted, 40 responded (11.7%), an d 39 patients were eligible. A total of 77% of respondents acknowledged receiving the PIB, of which...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research
AbstractAnaplastic lymphoma kinase (ALK) rearrangements have been reported in 5% to 6% of non ‐small cell lung cancer (NSCLC) patients. However, the concurrent existence of twoALK fusions within the same patient have rarely previously been reported. Moreover, considering the diversities ofALK mutations, it is necessary to evaluate the response of both double and new types ofALK fusions to ALK ‐tyrosine kinase inhibitors (ALK‐TKIs). Here, we report a case of a 64‐year‐old Chinese woman who was diagnosed with lung adenocarcinoma (ADC) who concurrently harbored two types ofALK‐rearrangements, including an unreport...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
Authors: Choo JR, Soo RA Abstract INTRODUCTION: The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic (gene) activations including anaplastic lymphoma kinase (ALK)-rearrangements. Despite remarkable initial responses, patients develop progressive disease via various resistance mechanisms, some of which are ALK dependent. Various next-generation ALK TKIs have been developed to improve on central nervous system (CNS) activity and also target the multitude of acquired resistance mechanisms. Of these, lorlatinib has the greatest s...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
Rearrangements in ROS1 oncogene, reported in 1 –2% of patients with non-small cell lung cancer (NSCLC), define a separate molecular sub-group of NSCLC [1]. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with the ability to cross the blood-brain barrier and have sub-nanomolar enzymatic efficacy in ta rgeting rearrangements in ALK and ROS1 [2]. ROS1 G2032R has been reported as the most commonly acquired mutation that mediates resistance to crizotinib therapy [3–5]; however, mechanisms that mediate lorlatinib resistance among patients with ROS1 rearrangement are rarely reported.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
ConclusionsThis study indicated that CT ‐707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose‐expansion phase recruitment has started.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
There was a case report showed that a novel pleckstrin homology and RUN domain containing M2 (PLEKHM2)- anaplastic lymphoma kinase (ALK) gene rearrangement in small cell lung cancer (SCLC) patient had long-term benefit from ALK inhibitors [1]. Actually, the case report demonstrated that next generation sequence (NGS) maybe a very useful method for detecting a new subtype of ALK fusion and it may provide a better understanding of ALK- tyrosine kinase inhibitors (TKIs) treatment. Here, we identified a novel type of ALK rearrangement responding to ALK inhibitors in non-small cell lung cancer (NSCLC) by NGS.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Authors: Indini A, Rijavec E, Ghidini M, Bareggi C, Gambini D, Galassi B, Antonelli P, Bettio G, Di Nubila C, Grossi F Abstract Introduction: Anaplastic lymphoma kinase (ALK) inhibitors are potent oral anti-cancer agents acting as tyrosine kinase inhibitors (TKIs), which are approved for the treatment of ALK+ non-small cell lung cancer (NSCLC). Over the last years, several new molecules have been developed and are currently under clinical investigation.Areas covered: In this paper, the authors review the most relevant clinical findings of ALK inhibitors in the treatment of ALK+ NSCLC. The authors discuss difference...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
Lung cancer is the leading cause of cancer death in the developed world. Targeted therapy in non-small cell lung cancer (NSCLC) reshaped the landscape of thoracic oncology. Among numerous identified driver mutations in NSCLC, several genetic abnormalities - resulting in activated and/or overexpressed oncoproteins (including EGFR, ALK, ROS1, BRAF) - are already druggable [1]. A paracentric chromosomal inversion (inv(2)(p21;p23)) affecting the genes echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK), both located on the short arm of chromosome 2 is one such abnormality that is detect...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Among patients with non-small cell lung cancer (NSCLC), it is estimated that between 3 –5% have anaplastic lymphoma kinase (ALK)-positive disease [1] and 1.7–2.2% have ROS1 gene rearrangement [2–4]. Targeting ALK using tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of patients with ALK-rearranged NSCLC [5]. However, most patients relapse on first or se cond-generation ALK TKI therapy within months to a few years following acquired resistance [6–8]. The third-generation ALK and ROS1 inhibitor lorlatinib (PF-06463922) was developed to inhibit resistant ALK mutations, includi...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Approximately 2% to 8% of patients with metastatic nonsquamous non –small-cell lung cancer (NSCLC) harbor a rearrangement in the anaplastic lymphoma kinase (ALK) gene in their tumors that may render them susceptible to targeted treatment with tyrosine kinase inhibitors [1–5]. Patients with ALK-rearrangements have been described as being younger, having a histor y of never or light smoking, and being likely to have adenocarcinoma with signet ring or acinar histology, based on previous studies [3,4,6].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
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