When and how to deal with brigatinib resistance

Brigatinib (Brigatinib) is a targeted drug used to treat ALK-positive non-small cell lung cancer (NSCLC). It has achieved good clinical efficacy due to its strong penetrating power and inhibitory effect on multiple ALK drug-resistant mutations. However, with the prolongation of treatment time, the problem of drug resistance gradually appears and becomes an important factor affecting the sustained efficacy of patients.

Generally speaking, brigatinib resistance usually appears between 12 months and 24 months after treatment, but the specific time varies depending on individual patient differences, tumor heterogeneity and treatment background. The mechanism of drug resistance is complex, mainly including secondary mutations in the ALK gene, activation of bypass signaling pathways, and phenotypic transformation of tumor cells. These changes reduce or render ineffective the inhibitory effect of brigatinib on tumor cells.

To respond to brigatinib resistance, the first step is to clarify the resistance mechanism through molecular testing. For patients who are found to have secondary ALK mutations, they can consider switching to next-generation ALK inhibitors that target specific mutations, such as Lorlatinib (Lorlatinib). In addition, some patients can be combined with chemotherapy or immunotherapy to enhance the therapeutic effect. After drug resistance occurs, clinicians should consider the patient's specific situation and choose an individualized treatment plan.

Finally, with in-depth research on the mechanisms of drug resistance, new targeted drugs and combination drug regimens continue to emerge, providing more possibilities for delaying drug resistance and improving patient prognosis. Patients should closely monitor changes in their condition during medication, and conduct timely review and evaluation to ensure that treatment plans can be quickly adjusted when drug resistance occurs and to maximize progression-free survival and overall survival.

Reference: https://go.drugbank.com/drugs/