Which generation of targeted drugs does Osimertinib (Tagrisso) belong to and its target description

Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI ), mainly developed for patients with EGFR mutated non-small cell lung cancer (NSCLC). Compared with the first and second generation EGFR-TKIs, third-generation drugs have significant advantages in selectivity and suppression of drug-resistant mutations, and can simultaneously suppress sensitive mutations (such as Exon 19deletions, L858R point mutations) and drug resistance mutations (the most common T790Mmutation), thus delaying disease progression.

The target of Osimertinib is mainly EGFR mutation-positive tumor cells. It irreversibly binds to the EGFR tyrosine kinase site and blocks the abnormal activation of the downstream RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways, thereby inhibiting the proliferation of tumor cells, promoting apoptosis and reducing tumor angiogenesis. Due to its high selectivity for the T790M resistance mutation, osimertinib can effectively overcome the resistance problems that arise during the treatment of first- and second-generation EGFR-TKI.

Compared with earlier EGFR-TKI, osimertinib performed better in controlling central nervous system (CNS) metastasis. It has good blood-brain barrier penetration ability and can inhibit the growth of brain metastases, which is especially important for patients with advanced NSCLC. Studies have shown that the response rate and survival benefit of osimertinib in patients with brain metastases are significantly better than those of first- and second-generation EGFR-TKI.

In clinical application, osimertinib is not only used for the second-line treatment of T790M mutation-positive relapsed or metastatic NSCLC, but is also approved as a first-line drug for the initial treatment of EGFR-sensitive mutations. Its identity and target specificity as a third-generation targeted drug give it significant advantages in drug resistance management, extending progression-free survival and improving quality of life, making it a EGFR mutantAn important standard treatment option for patients with NSCLC.

Reference materials:https://www.drugs.com/