The incidence of brain metastasis (BM) is high in patients with non-small-cell lung cancer. Available standard therapeutic options, such as whole-brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. Novel agents, such as EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs), have now been included in standard non-small-cell lung cancer treatments. In a small subset of patients harboring EGFR-activating mutations, erlotinib and gefitinib administration was followed by a response rate of 70–80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. However, since most of the larger studies on these agents have excluded BM patients from their series, few prospective data are available on the efficacy of these agents in this setting. In recent years, however, several authors have reported a growing number of cases of partial and complete response in BM patients treated with EGFR TKIs. Data from retrospective series and Phase II studies also suggest that a response can be obtained using EGFR TKI treatment for patients with BM, especially those harboring EGFR mutations. 相似文献
Non-small-cell lung cancer (NSCLC) is a heterogeneous illness associated with a high mortality rate. Personalized therapy may improve treatment outcomes by identification of a specific genotypic anomaly and target-specific therapy. The most significant development in recent years was the discovery of activated EGF receptor (EGFR) mutations at exons 19 and 21. Patients with EGFR mutations respond dramatically to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib, resulting in longer progression-free survival. Multiple randomized studies, including the Iressa Pan-Asia Study and WJTOG3405, have confirmed the role of EGFR tyrosine kinase inhibitors as standard first-line therapy for patients with the EGFR mutation. In this article, we summarize the current nonpersonalized therapies and examine the available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, or metastatic disease. 相似文献
Inhibition of the epidermal growth factor receptor is one of the most promising novel therapeutic strategies to be used in the treatment of patients with non-small cell lung cancer. A number of compounds that target the epidermal growth factor receptor are in an advanced stage of clinical development including both antibodies directed against the receptor and small molecule inhibitors of epidermal growth factor receptor tyrosine kinase activity. This drug profile focuses on the development of erlotinib, an orally available inhibitor of epidermal growth factor receptor tyrosine kinase. Results of clinical trials are reviewed, two trials of erlotinib in combination, one with paclitaxel and carboplatin, the other with gemcitabine and cisplatin, and the National Cancer Institute of Canada – Clinical Trials Group BR21, the first study to demonstrate a survival benefit for this class of compound in non-small cell lung cancer. The future role of erlotinib in the management of patients with non-small cell lung cancer is also discussed. 相似文献
Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.
Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.
Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years. 相似文献