Objectives: The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non-small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations.
Materials And Methods: Electronic records of patients with EGFR-mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.
Results: Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval [CI]: 27.7-45.6) in group A and 20.8 months (95% CI: 19.4-24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0-13.9) overall and 15.7 months (95% CI: 13.9-17.3) in group A. The 2- and 3-year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively.
Conclusion: Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies.
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http://dx.doi.org/10.1002/cam4.4127 | DOI Listing |
Am J Transl Res
November 2024
Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University Kunming 650032, Yunnan, China.
Objectives: This study aims to elucidate the role of cAMP responsive element binding protein 3 like 4 (CREB3L4) in the pathogenesis of lung adenocarcinoma (LUAD) and to provide new insights and approaches for its effective treatment. An analysis was conducted on the expression and prognostic implications of CREB3L4 in LUAD.
Methods: Potential downstream target genes regulated by CREB3L4 were identified through chromatin immunoprecipitation assay sequencing and mRNA sequencing analyses, and the regulatory relationship, mechanism, and prognostic significance of the identified target gene in LUAD were subsequently confirmed.
Transl Lung Cancer Res
November 2024
Department of Respiratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
Background: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for -mutated non-small cell lung cancer (NSCLC). However, there is no established treatment for osimertinib resistance, so second-generation afatinib is an alternative treatment option. The purpose of this study was to elucidate gene alterations associated with afatinib efficacy and resistance by analyzing cell-free DNA (cfDNA) obtained from patients with -mutated NSCLC.
View Article and Find Full Text PDFOncol Lett
February 2025
Department of Thoracic Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China.
For patients with advanced non-small cell lung cancer (NSCLC) that have epidermal growth factor receptor () mutations, EGFR tyrosine kinase inhibitors (TKIs) are the standard treatment and have significant clinical benefits. Third-generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR-sensitizing mutation-positive and T790M-positive. Despite the efficacy of third-generation TKIs, patients inevitably develop resistance and the resistance mechanisms are heterogeneous.
View Article and Find Full Text PDFThorac Cancer
December 2024
Department of Chemotherapy, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.
Introduction: First-line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR-tyrosine kinase inhibitor (TKI) is often performed after first-line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR-TKI rechallenge after first-line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR-TKI rechallenge with another TKI.
View Article and Find Full Text PDFCytokine
January 2025
Ningde Clinical Medical College of Fujian Medical University, Ningde, Fujian 352100, China; Clinical Pharmacy, Ningde Municipal Hospital of Ningde Normal University, Ningde, Fujian 352100, China; Collaborative Innovation Center of Active Ingredient Research of She Medicine(2020Z03), Ningde Normal University, Ningde, Fujian 352100, China; Innovation Center of Clinical Pharmacy Service(2023T06), Ningde Normal University, Ningde, Fujian 352100, China. Electronic address:
The epidermal growth factor receptor (EGFR) signaling pathway is crucial for skin barrier integrity and immune response. This study explores the impact of EGFR inhibitors, osimertinib and afatinib, on keratinocyte function, focusing on keratin (KRT1, KRT17) and tight junction protein (CLDN1, CLDN2, CLDN4) expression in HaCaT cells. Osimertinib significantly increased the mRNA and protein levels of keratins and inflammatory markers, IL-6 and TNF-α, via activation of the EGFR-STAT3 signaling pathway.
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