Dacomitinib/Dacomitinib: Leading a new era of second-generation EGFR targeted drug treatment

Dacomitinib/Dacomitinib (Dacomitinib), known as an outstanding representative of the second generation of targeted drugs, has been approved by the U.S. Food and Drug Administration (FDA) and has become a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) carrying EGFR Del19 or exon 21 L858R mutations. As a multi-target protein kinase irreversible inhibitor developed by Pfizer, it exhibits excellent anti-cancer effects by effectively inhibiting the protein tyrosine kinase activity of cancer cells.

Compared with first-generation targeted drugs, dacomitinib brings new hope to patients with its higher therapeutic effect and relatively fewer side effects. It exhibits significant antitumor activity in vitro and in xenograft models by potently and irreversibly inhibiting the pan-human epidermal growth factor receptor (HER) family, specifically EGFR, ErbB2, and ErbB4.

It is worth mentioning that dacomitinib has demonstrated strong inhibitory ability when dealing with cell lines carrying theL858R/T790M mutation. These cell lines are usually resistant to first-generation TKIs such as gefitinib, while dacomitinib can effectively inhibit their proliferation, with an IC50 value much lower than gefitinib. In addition, dacomitinib also inhibited the proliferation of cells expressing T790M in cis in different deletions of exon 19, further demonstrating its broad inhibitory effect.

As an irreversible inhibitor, dacomitinib has a longer duration of efficacy than first-generationTKIs, thanks to its good pharmacokinetic properties, including high oral bioavailability, high distribution volume and long half-life. These properties make dacomitinib an important treatment option for patients with NSCLC.

In general, dacomitinib, with its excellent therapeutic effect and unique pharmacological properties, has led a new era of second-generationEGFR targeted drug treatment, bringing more treatment options and hope to NSCLC patients.