Which generation of targeted drug is dacomitinib? What are its advantages and differences compared with other generation targeted drugs?

Dacomitinib is a second-generation targeted drug mainly used to treat patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Unlike the first-generation EGFR-targeted drugs (such as erlotinib and gefitinib), dacomitinib is an irreversible EGFR tyrosine kinase inhibitor (TKI) that can inhibit both the mutant and wild-type EGFR, thereby more effectively preventing the growth and spread of cancer cells. The biggest feature of the second generation of targeted drugs is that they overcome the problem of drug resistance through stronger inhibitory effects and are usually effective against more EGFR mutation types.

Compared with first-generation drugs, the advantage of dacomitinib is mainly reflected in its stronger anti-tumor activity. Most of the first-generation drugs work well in EGFR mutation-positive patients, but as treatment progresses, patients often develop drug resistance, especially against drug-resistant mutations such as T790M mutation. Dacomitinib, on the other hand, has a stronger targeting effect and longer duration of efficacy, and can overcome the resistance caused by some first-generation drugs, so it may have a more significant effect when treating patients in the advanced stage.

Compared with third-generation targeted drugs (such as osimertinib), although dacomitinib does not have the specific inhibitory effect of osimertinib on T790M mutations, it has excellent inhibitory effect on all types of EGFR mutations. Third-generation targeted drugs are usually more specific against T790M resistance mutations, while dacomitinib is a broad-spectrum EGFR inhibitor that can effectively treat other types of EGFR mutation-positive non-small cell lung cancer. It may still have significant advantages for patients without the T790M mutation.
Although dacomitinib has strong efficacy in the treatment of non-small cell lung cancer, its side effects are more obvious compared with other targeted drugs. Common side effects include diarrhea, rash, mouth ulcers, etc. These side effects may affect the patient's quality of life. Therefore, proper side effect management needs to be carried out under the guidance of a doctor when using dacomitinib. Overall, dacomitinib, as a second-generation EGFR-targeted drug, provides a more effective treatment option for some patients with non-small cell lung cancer, especially showing unique advantages in the treatment of drug-resistant or relapsed patients.
Reference: https://www.pfizer.com/products/product-detail/vizimpro