Neuroendocrine carcinoma (NEC), a subtype of neuroendocrine tumors with high proliferative activity, is characterized by strong invasiveness and poor prognosis. This article reports a previously healthy female non-smoker who developed NEC occurring sequentially in different lobes of both lungs. The lesions were pathologically diagnosed by hematoxylin-eosin (HE) staining as large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), respectively. Next-generation sequencing (NGS) performed on both lesions revealed the presence of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion mutations in both lesions. Notably, the patient achieved a significant therapeutic response to ALK-tyrosine kinase inhibitors (TKIs) targeted therapy.
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Humans ; Oncogene Proteins, Fusion/metabolism* ; Female ; Lung Neoplasms/enzymology* ; Carcinoma, Neuroendocrine/pathology* ; Middle Aged

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/adverse effects* ; Aged ; Antineoplastic Agents/adverse effects*

The discovery of anaplastic lymphoma kinase (ALK) tyrosine kinase gene rearrangement mutations in non-small cell lung cancer (NSCLC) has driven continuous advancements in ALK-targeted therapies. The next generation of ALK tyrosine kinase inhibitor, Brigatinib, has demonstrated significant efficacy in patients with ALK-positive NSCLC, offering clinical benefits in deep response of tumor, treatment of brain metastases patients, quality of life, and long-term survival. This review will provide current advancements and exploratory directions for Brigatinib.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; Pyrimidines/therapeutic use* ; Organophosphorus Compounds/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Epidermal growth factor receptor (EGFR) exon 20 mutations represent a rare subset of genetic alterations in non-small cell lung cancer (NSCLC). Among them, the complex mutation H773_V774delinsLM is exceedingly uncommon, accounting for only 0.2%-1% of all EGFR mutations. It is currently believed that rare EGFR mutations are generally resistant to the first- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although the third-generation EGFR-TKIs have shown some efficacy in certain rare mutations, clinical evidence regarding their use in NSCLC patients with the H773_V774delinsLM mutation remains sparse, and their efficacy and safety are yet to be clarified. Here, we present the first documented case of a patient with EGFR H773_V774delinsLM-mutant lung adenocarcinoma who experienced remarkable tumor regression following treatment with furmonertinib. This case highlights the potential utility of furmonertinib in treating patients with this rare EGFR mutation and may provide valuable insight into emerging treatment strategies for similarly affected patients.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Exons/genetics* ; Lung Neoplasms/enzymology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

Lung cancer represents one of the most prevalent malignant tumors globally, and its treatment has entered the era of targeted therapy. The epidermal growth factor receptor (EGFR) mutation is a common type of genetic mutation in non-small cell lung cancer (NSCLC), while c-ros oncogene 1 receptor tyrosine kinase (ROS-1) fusion mutation is a rare mutation site. Currently, there are few case reports on the coexistence of EGFR and ROS-1 gene mutations. This study reports a case of NSCLC with coexisting EGFR and ROS-1 gene mutations, aiming to provide relevant treatment strategies for clinical practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/genetics* ; Mutation ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; Male ; Middle Aged ; Female

Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Anaplastic Lymphoma Kinase/antagonists & inhibitors* ; Lung Neoplasms/enzymology* ; Neoadjuvant Therapy/methods* ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use*

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
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Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; China ; Diarrhea ; etiology ; ErbB Receptors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Liver Diseases ; etiology ; Lung Diseases ; etiology ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Stomatitis ; etiology

With the development of sequencing technology, the detection rate of de novo T790M mutation is increasing. The emergence of the third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide treatment opportunities. Secondary T790M mutation is often emphasized in clinic, but de novo T790M mutation is neglected. This review found that the incidence of de novo T790M mutation fluctuated greatly, which was mainly affected by sequencing techniques. The de novo T790M mutation is mainly low in mutation abundance, easy to combine with other gene changes, a poor predictor and prognostic factor and the efficacy of the first and second generation EGFR-TKIs is limited. The therapeutic value of osimertinib needs to be studied.
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Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; enzymology ; genetics ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; enzymology ; genetics ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated some dramatic efficacy in advanced non-small-cell lung cancer (NSCLC) patients with activating EGFR mutation. However, progression-free survivals (PFS) among those patients who were treated with first line EGFR TKIs were inconsistent. The aim of this study is to explore the association of clinical prognostic factors with EGFR-TKI efficacy in advanced NSCLC patients. METHODS: The demographic and clinical characteristics of 203 patients with activating EGFR mutation treated with first generation TKI as a first-line therapy were retrospectively reviewed. RESULTS: Of the 203 patients enrolled in this study, 139 patients had progression of disease and 63 patients died. The subjects had a median follow up duration of 21.1months and a median PFS of 14.3 months. Partial response (PR) was achieved in 127 (66.1%) patients and stable disease (SD) rate was achieved in 55 (28.6%) patients. In univariate analysis, patients with 2 or higher ECOG score (5.1 vs 16 months, P=0.033), SD as best overall response (9.5 vs 17.9 months, P=0.030), extrathoracic metastasis (11.7 vs 27.5 months, P=0.004), liver metastasis (4.1 vs 16.0 months, P=0.000), bone metastasis (13.3 vs 21.5months, P=0.027) and pulmonary embolism (5.5 vs 16.6 months, P=0.005) had shorter PFS than those without the listed factors. Multivariable Cox regression analysis showed best overall response (HR=1.825, 95%CI: 1.107-3.008, P=0.018) and liver metastasis (HR=1.694, 95%CI: 1.146-5.756, P=0.022) were independent predictive factors of shorter PFS. CONCLUSIONS Despite the high efficacy of EGFR-TKI, SD as best overall response and liver metastasis predicts poorer PFS in advanced NSCLC patients with EGFR gene mutations receiving first-line therapy treatment.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; mortality ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

PURPOSE: Previous retrospective studies suggest that anaplastic lymphoma kinase (ALK) mutation-positive (ALK+) non-small cell lung cancer (NSCLC) patients are sensitive to pemetrexed. To determine its efficacy, we retrospectively evaluated clinical outcomes of pemetrexed-based chemotherapy in patients with ALK+ NSCLC. MATERIALS AND METHODS: We identified 126 patients with advanced, ALK+ NSCLC who received first-line cytotoxic chemotherapy. We compared response, progression-free survival (PFS), and overall survival (OS) rates according to chemotherapy regimens. Furthermore, we evaluated intracranial time to tumor progression (TTP) and proportion of ALK+ cells as prognostic factors. RESULTS: Forty-eight patients received pemetrexed-based chemotherapy, while 78 received other regimens as first-line treatment. The pemetrexed-based chemotherapy group showed superior overall response (44.7% vs. 14.3%, p < 0.001) and disease control (85.1% vs. 62.3%, p=0.008) rates. The pemetrexed-based chemotherapy group also exhibited longer PFS (6.6 months vs. 3.8 months, p < 0.001); OS rates were not significantly different. The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS. Intracranial TTP was similar between the treatment groups (32.7 months vs. 35.7 months, p=0.733). Patients who harbored a greater number of ALK+ tumor cells (≥70%) showed prolonged OS on univariate analysis (not reached vs. 44.8 months, p=0.041), but not on multivariate analysis (hazard ratio: 0.19, 95% confidence interval: 0.03–1.42; p=0.106). CONCLUSION: Pemetrexed-based regimens may prolong PFS in patients with ALK+ NSCLC as a first-line treatment, but are not associated with prolonged OS. Exposure to second-generation ALK inhibitors may improve OS rates in patients with ALK+ NSCLC.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/mortality ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/*drug therapy/enzymology/mortality ; Male ; Middle Aged ; Mutation ; Pemetrexed/*therapeutic use ; Receptor Protein-Tyrosine Kinases/genetics ; Retrospective Studies ; Survival Rate ; Treatment Outcome