Erlotinib belongs to several generations of targeted drugs. What are its characteristics?

Erlotinib (Erlotinib) is a first-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) and is a classic EGFR-targeted drug developed in the early stage along with gefitinib. Its main mechanism is to reversibly bind to the EGFR tyrosine kinase domain and inhibit the activation of signaling pathways, thereby interfering with the proliferation, migration and anti-apoptosis processes of tumor cells. As a first-generation drug, erlotinib has a good inhibitory effect on EGFR-sensitive mutations (such as exon 19 deletion and exon 21 L858R mutation) and is widely used in the targeted therapy of non-small cell lung cancer.

The advantages of erlotinib are that it is convenient to take, has a rapid onset of action, and has clear efficacy in the mutant population. It especially shows a high response rate in Asian patients. However, as a first-generation TKI, it also has certain limitations. The first is the widespread problem of drug resistance. Almost all patients who receive treatment will develop acquired drug resistance after about 9 to 13 months, the most common of which is the EGFR T790M mutation. Secondly, for patients with EGFR wild-type or atypical mutations, erlotinib has limited effect and should be used with caution. In addition, adverse reactions such as rash, diarrhea, stomatitis, etc. are also common, and the dose needs to be adjusted according to the patient's tolerance.

With the development of targeted drugs, second-generation (such as afatinib) and third-generation (such as osimertinib)EGFR-TKIs have come out one after another. In comparison, erlotinib has gradually been replaced in terms of treatment breadth and resistance management. However, in areas where resources are limited and genetic testing is not yet popular, erlotinib is still widely used as first-line or alternative treatment for EGFR mutation-positive NSCLC due to its low price and rich clinical experience. In the future, combined with molecular typing, liquid biopsy and new combination therapies, erlotinib will still have certain value in the precision medicine system.

Reference materials:https://en.wikipedia.org/wiki/Erlotinib