Which generation of targeted drugs is Osimertinib/Tagrisso? What is the difference between it and other generations?

Osimertinib/Tagrisso (Osimertinib) is a third-generation targeted drug and a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). After EGFR acquires the secondary T790M mutation that confers resistance to first- and second-generation drugs, it still irreversibly inhibits its activity, and its efficacy has been verified in patients whose tumors develop T790M-mediated resistance and in the first-line treatment of patients with EGFR mutation-positive non-small cell lung cancer.

Osimertinib is an irreversibleT790M mutation-specific EGFR-TKI with little inhibitory activity against wild-type EGFR and was developed to overcome T790M-mediated acquired resistance to first- or second-generation EGFR-TKIs. The U.S. Food and Drug Administration (FDA) approved osimertinib as an 80 mg once-daily tablet for the treatment of patients with EGFR T790M-positive metastatic non-small cell lung cancer (NSCLC) who have progressed during or after prior EGFR-TKI therapy.

Compared with first- and second-generation drugs targeting EGFR mutations, osimertinib is more selective and can inhibit EGFR kinase activity more effectively. This means that osimertinib can target malignant tumor cells more effectively and reduce damage to normal cells, thereby improving treatment efficacy and reducing side effects. In addition, osimertinib has good blood-brain barrier permeability. This means that it can cross the blood-brain barrier and also has a certain effect on brain metastases caused by EGFR mutations, providing a new treatment option for NSCLC patients with EGFR mutations. In contrast, the first two generations of targeted drugs were less effective in treating brain metastases.

Therefore, osimertinib is a third-generation EGFR-TKI. Compared with the first two generations of targeted drugs, the third-generation targeted drugs have some unique characteristics and advantages.