Which generation of targeted drug is crizotinib? Why is it said to be first or second generation?

Crizotinib, as the first-generation ALK inhibitor, has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC). A generation of targeted drugs are usually the first to appear, and they inhibit the growth and spread of tumors by interfering with specific cancer cell signaling pathways. Crizotinib, as a tyrosine kinase inhibitor, is mainly used to treat certain non-small cell lung cancer and lymphoma, and is one of the first targeted drugs to be developed and applied clinically.

The PROFILE 1014 study compared crizotinib with chemotherapy in 343 patients with previously untreated advanced non-small cell lung cancer. They were randomized to receive crizotinib or pemetrexed plus platinum (cisplatin or carboplatin). The progression-free survival times of the crizotinib group (172 cases) and the chemotherapy group (171 cases) were 10.9 months and 7.0 months respectively. The ORR in the crizotinib group was 74%, while the ORR in the chemotherapy group was 45%. At the time of reporting, median OS had not been reached in either group, with estimated 1-year survival rates of 84% for crizotinib and 79% for chemotherapy. However, treatment with crizotinib is not without risks. Drug-related adverse events include visual disturbances, digestive complaints such as diarrhea and nausea, and symptoms such as edema.

Second-generation targeted drugs refer to drugs that are improved and optimized on the basis of first-generation targeted drugs. They are often more targeted and less toxic to improve treatment effectiveness. Although crizotinib has been called a first-generation targeted drug to some extent, with the advancement of science and technology, more advanced second- and even third-generation targeted drugs are emerging, bringing better treatment options to cancer patients.