The shortest time for resistance to osimertinib (Tagrisso) to appear in the first line

Osimertinib, as a third-generation EGFR-TKI, is commonly used for the first-line treatment of EGFR mutation-positive non-small cell lung cancer. It was originally designed to overcome the resistance problem of first- and second-generation EGFR inhibitors, especially the T790M mutation. However, even if it is used as a first-line drug, some patients may still develop resistance within a short period of time. Clinical data show that the time for drug resistance to appear varies depending on individual differences, tumor load and molecular characteristics, but early signs of drug resistance can appear as early as about 6 months.

The mechanisms of drug resistance are diverse, including acquired EGFR mutations (such as C797S), MET amplification, HER2 amplification or small cell transformation. These molecular changes will reduce the inhibitory effect of osimertinib on EGFR and allow tumor cells to continue to proliferate. Early drug resistance usually manifests as the original lesions shrinking and then gradually stagnating, or some lesions progress while other lesions are still sensitive to drugs. Imaging and molecular testing can provide early warning before the emergence of drug resistance and provide a basis for subsequent treatment decisions.

In clinical practice, in order to delay drug resistance as much as possible, doctors will recommend regular review of imaging and hematology indicators, and if necessary, perform liquid biopsy or tissue biopsy to monitor the mutation status. If signs of resistance are found, a combination treatment strategy can be selected based on the type of resistance, such as combining MET inhibitors, angiogenesis inhibitors or chemotherapy to prolong the patient's effective control period on osimertinib. Patients should pay attention to changes in symptoms while taking the medicine, and promptly report any abnormalities such as cough, chest pain or dyspnea so that the efficacy can be evaluated as early as possible.
Although resistance to osimertinib may appear earlier, its overall progression-free survival (PFS) in first-line use is still significantly better than that of the first-generation EGFR-TKI, and most patients can still achieve effective control for more than 8-18 months. Through regular monitoring, individualized adjustment and early combined intervention, the benefits of first-line treatment with osimertinib can be maximized, while providing a time window for the next treatment after drug resistance, and achieving long-term management of EGFR-mutated non-small cell lung cancer.
Reference: https://www.drugs.com/