Small molecule targeted drugs of EGFR gene in non-small cell lung cancer
EGFR gene target
EGFR driver gene mutations and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted drugs as the representative of targeted therapy, for advanced EGFR positive non-small cell lung cancer patients to improve the survival time and quality of life. In the past, the clinical treatment of advanced lung cancer is very limited, usually for systemic palliative chemotherapy and local palliative radiotherapy, there are a variety of problems, including low control rate, adverse reactions, short survival of patients. Compared with the past, EGFR-TKI treatment of patients with advanced non-small cell lung cancer has the advantages of progression-free survival (PFS) benefit and good tolerance, and has become the first-line treatment of advanced non-small cell lung cancer.
EGFR-TKI
EGFR-TKI is a small molecule EGFR inhibitor, which controls the activation of tyrosine kinase through the endogenous ligand competitive binding to EGFR, blocks the EGFR signaling pathway, and inhibits the proliferation and metastasis of tumor cells. For EGFR-positive patients, the use of EGFR-KTI drugs can significantly prolong survival. EGFR-TKI can be divided into the first generation, the second generation and the third generation according to the different drug binding characteristics and action sites [3].
1. The first generation of EGFR-TKI reversibly inhibits the tyrosinase activity of EGFR. Gefitinib, erlotinib and icotinib are the representative drugs;
2. The second-generation EGFR-TKI irreversibly inhibits the tyrosinase activity of EGFR and inhibits other members of the ERBB family. Dacomitinib and Afatinib are the representative drugs;
3 and the third generation EGFR-TKI are that they are effective in 1. the T790M mutation of EGFR exon 20 of the second generation drug resistance target, and are more likely to pass through the blood brain barrier. Osimertinib, alametinib, and vormetinib are representative drugs.
Related Messages
Chinese Society of Clinical Oncology (CSCO)2020 guidelines point out that for patients with stage IV EGFR sensitive mutation non-small cell lung cancer, gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib can be used as grade I recommend for first-line treatment.
China's original three-generation EGFR-TKI alametinib showed excellent efficacy in the first-line and post-line treatment of EGFR sensitive mutation bureau late or advanced NSCLC. The 2021 version of the guidelines will raise alametinib to grade I recommend for the second-line treatment of advanced NSCLC with the T790M mutation that has failed first-or second-generation EGFR-TKI therapy. Since alametinib has not yet been approved as a first-line indication for NSCLC, the 2021 version of the guidelines added it as a level II recommend for first-line treatment of EGFR sensitive mutations.
In addition, vametinib is also the third generation EGFR-TKI drug originally developed in China. The 2020 American Society of Clinical Oncology (ASCO) Conference announced that the results of Phase IIB clinical studies after the first generation and second generation EGFR-TKI resistance of NSCLC with EGFR mutation showed good curative effect, and was approved as an indication in 2021 and a Class II recommend for post-line treatment of EGFR sensitive mutation in the new version of the guidelines.
Adjuvant targeted therapy brings hope for long-term high-quality survival of early and middle-term lung cancer patients with positive EGFR gene mutation in China. The 2021 guideline added: osimertinib (after adjuvant chemotherapy) or icotinib adjuvant therapy for patients with positive EGFR sensitive mutations in stages IIA, IIB and IIIA as a grade I recommend [3].
Conclusion
lung cancer has developed from the traditional radiotherapy and chemotherapy mode to the precise treatment mode including anti angiogenesis, targeting and immunity. The new guidelines update a variety of targeted drugs for drive gene-positive NSCLC patients, as well as domestic original immune drug treatment strategies for non-drive gene NSCLC patients. More and more domestic original research drugs are written into the guidelines, highlighting the research and innovation capabilities of Chinese researchers and Chinese pharmaceutical companies. In the future, it is expected that China's lung cancer research will have more innovative data of its own, which will strongly promote and lead the domestic original research drugs to the world stage.
References
[1] Wang Yajie, Chen Peng. Research progress of EGFR-TKIs combined with chemotherapy in EGFR positive advanced non-small cell lung cancer [J]. Journal of Clinical Pulmonary Science, 2022, 27(1):5.
[2] Li Wangzhen, Cai Yongguang. Application status and progress of EGFR-TKI in the treatment of EGFR mutant non-small cell lung cancer [J]. Clinical medical research and practice.
[3] Shao Chuchu, Wang Wanying, Ren Shengxiang. Interpretation of CSCO Guidelines for Diagnosis and Treatment of Non-small Cell Lung Cancer (2021 Edition) [J]. Journal of Tongji University: Medical Edition, 2022, 43(1):9.
Disclaimer: This article is for the purpose of information exchange only, and the views expressed in this article do not represent the position of Zhongyi, nor do they represent support or opposition to the views expressed in this article. This article is not a treatment plan recommend, if you need to get treatment plan guidance, please go to a regular hospital.
Copyright Description: The content of this message, including some pictures, is collected from the Internet. Foreign content is translated and edited. The text content is only used for learning, communication, research or appreciation, and non-profit purposes. If you have any copyright problems, please contact us and delete them.
