Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Lorlatinib is a potent third-generation ALK tyrosine kinase inhibitor (TKI). CROWN study demonstrated remarkable efficacy and manageable toxicity of first-line lorlatinib treatment for advanced non-small cell lung cancer (NSCLC) with ALK rearrangements. However, only 10 ALK-positive NSCLC patients were randomized to the lorlatinib group in China mainland. There is a vast vacancy of efficacy and safety regarding first-line lorlatinib treatment in China advanced ALK-positive NSCLC. Additionally, understanding of the benefit-risk profile of lorlatinib in a broader population and real-world data of diversity of ALK-TKIs are limited.
Patients And Methods: We adopted a patient-centric trial (PCT) design to provide more generalizable data to better inform clinical decision-making. This is a 3 cohorts, open-label, multicenter, phase II study (CTONG2203), conducted to prospectively enroll 189 treatment-naïve patients with advanced ALK-positive NSCLC in China, which was divided into 2 treatment intervention cohorts and real-world observing (RO) cohort. The treatment intervention cohorts include restrictive eligibility criteria "CROWN criteria (CC) cohort," and broadening eligibility criteria "Expand Eligibility Criteria (EC) cohort," who will receive first-line lorlatinib treatment. And we concomitantly set up a prospective RO cohort to observe the clinical outcomes of these patients treated with different ALK-TKI who received physician's therapy of choice.
Conclusion: This patient-centric study will contribute data on efficacy, safety and resistance mechanism of first-line lorlatinib, and offer better perspectives on the current status of real-world treatment of ALK-TKIs in advanced ALK-positive NSCLC in China.
Clinical Trial Registration: NCT06092086 (CTONG 2203).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cllc.2025.05.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.
J Manag Care Spec Pharm
September 2025
Division of Medical Oncology, Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles.
Background: Alectinib, brigatinib, and lorlatinib are all preferred first-line (1L) therapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in National Comprehensive Cancer Network (NCCN) guidelines. Although clinical trials have demonstrated their efficacy, real-world evidence on treatment patterns, costs, and outcomes may help differentiate these therapies and inform optimal 1L treatment selection in the absence of head-to-head comparisons.
Objective: To evaluate real-world outcomes for patients with ALK+ NSCLC receiving 1L ALK tyrosine kinase inhibitors (TKIs), focusing on drug acquisition costs, health care utilization, and clinical outcomes.
Case Report: A rare case of ALK-KIF5B gene fusion benefited from treatment with lorlatinib.
Front Oncol
August 2025
Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
The anaplastic lymphoma kinase () gene encodes a transmembrane receptor tyrosine kinase. Most mutations in gene result from translocations with other genes, forming fusion oncogenes. To date, 21 different genes have been identified as fusion partners, each activating distinct signaling pathways that influence cancer cell proliferation, invasiveness, and tumorigenicity.
View Article and Find Full Text PDFCabozantinib overcomes ROS1 L2086F NSCLC resistance to lorlatinib: A case report.
Medicine (Baltimore)
August 2025
The Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen City, Guangdong Province, China.
Rationale: ROS1 rearrangement a distinct molecular subtype of non-small cell lung cancer that is amenable to targeted therapeutic interventions. Despite the availability of effective targeted therapies, the development of acquired resistance to later-line inhibitors, particularly lorlatinib, remains an inevitable, and clinically significant challenge. The emergence of the ROS1 L2086F mutation as a mechanism of lorlatinib resistance further complicates treatment, with limited therapeutic options available post-resistance.
View Article and Find Full Text PDFClinical Outcomes of Patients With Advanced ALK-Rearranged Lung Squamous Cell Carcinoma Treated With ALK Tyrosine Kinase Inhibitors.
Clin Lung Cancer
July 2025
Guizhou Medical University, Guiyang, Guizhou, China; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Department of Pathology, Immuno-Oncology L
Background: DNA-based next-generation sequencing (NGS) has identified ALK rearrangements in lung squamous cell carcinoma (LUSC), a subset of nonsmall cell lung cancer traditionally lacking effective targeted therapies. While ALK tyrosine kinase inhibitors (TKIs) like crizotinib and alectinib are effective in ALK-rearranged lung adenocarcinoma, their efficacy in LUSC remains poorly defined due to limited subtype-specific data.
Methods: We presented a case of ALK-rearranged LUSC and established a patient-derived xenograft (PDX) model to validate the tumor-inhibitory effects of various ALK-TKIs on ALK-positive LUSC.
Efficacy and safety analysis of lorlatinib for ALK-positive advanced NSCLC: a multicentre real-world study in China.
BMC Cancer
July 2025
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing, China.
Background: Lorlatinib, a third-generation Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKI), has demonstrated excellent curative effect in clinical studies to overcome mutations resistant to first- and second-generation ALK-TKIs. It also has improved blood-brain barrier crossing and reduced brain metastases.
Methods: 44 patients were selected who received Lorlatinib as initial treatment for first-diagnosis ALK-positive non-small-cell lung cancer (NSCLC) or who received Lorlatinib as a back-line treatment after developing resistance with first- and second-generation ALK-TKIs.