Can Osimertinib (Tagrisso) be continued to be used and its regimen after drug resistance?

Osimertinib is a third-generation EGFR-TKI that is mainly used for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Once drug resistance occurs, it means that tumor cells are activated through acquired mutations or alternative signaling pathways, reducing the effect of drug inhibition of EGFR. Whether to continue using osimertinib after drug resistance needs to be evaluated based on the patient's specific drug resistance type, disease progression rate, and overall physical condition. In the case of local progression or oligometastasis, some patients can continue to use osimertinib to control sensitive lesions, combined with local treatments.

Resistance mechanisms are diverse, including EGFR C797S mutation, METamplification, HER2amplification, small cell transformation or activation of alternative signaling pathways, etc. Treatment options vary for different types of drug resistance. For example, for patients with only local drug resistance or a small amount of disease progression, continued osimertinib treatment can be considered, while local intervention such as radiotherapy, surgery, or radiofrequency ablation can be performed to maintain control of sensitive lesions. This strategy can prolong progression-free survival and try to avoid immediate changes to systemic treatment regimens.

For patients who have progressed extensively or developed drug-resistant mutations, doctors often recommend switching to another treatment regimen. Optional strategies include chemotherapy, combined targeted drugs, or new EGFR inhibitors or combination treatments participating in clinical trials. For example, if METamplification is detected, combination of MET inhibitors can be considered; if C797S mutation occurs, the suitability of other experimental third- or fourth-generation EGFR inhibitors can be evaluated. At the same time, before switching regimens, liquid biopsy or tissue biopsy is performed to clarify the type of drug resistance, which will help formulate precise treatment plans.

In general, osimertinib drug resistance does not necessarily require discontinuation across the board. The key lies in individualized judgment based on the distribution of lesions, type of resistance, and the overall condition of the patient. Patients with local progression may continue osimertinib in conjunction with local therapy, whereas patients with widespread systemic progression need to be evaluated for alternatives or clinical trials. No matter which strategy is adopted, regular imaging and molecular testing are essential to promptly adjust treatment plans and achieve long-term careful management of NSCLC.

Reference materials:https://www.drugs.com/