Analysis of the time to develop resistance to serputinib/serpatinib (Ruitu)

In the field of targeted therapy, drug resistance is an almost unavoidable topic. Selpercatinib/selpercatinib, as a highly selective RET inhibitor, can usually bring about ideal disease control in the initial treatment phase. However, as the treatment time is prolonged, some patients with non-small cell lung cancer (NSCLC) and thyroid cancer may still face drug resistance problems. Judging from research and real-world experience, there is no fixed point in the resistance time of seprotinib, but is affected by multiple factors.

First of all, the occurrence of drug resistance is closely related to the genetic instability of the tumor itself. RET-driven tumors may circumvent RET inhibition by acquiring new genetic changes or activating alternative signaling pathways under continued drug pressure. This type of resistance is often acquired resistance, manifested by disease progression after a period of stable control.

Secondly, the patient's previous treatment history is also an important factor affecting the time of drug resistance. Overseas data show that patients who have received multiple lines of systemic therapy usually have higher tumor cell heterogeneity and are more likely to undergo adaptive changes during targeted therapy. Therefore, drug resistance may appear relatively earlier in such patients, and patients who are new to treatment or have fewer lines of treatment can often achieve more durable disease control.

It is worth noting that drug resistance is not the same as the drug "complete failure". In some cases, tumors may progress only locally or in individual lesions, while other sites remain sensitive to seputinib. In overseas clinical practice, for this type of "focal progression", local treatment combined with continued targeted medication is often used to try to extend the benefit time of the original regimen.

Overall, the occurrence of seprotinib resistance is a gradual process rather than a sudden event. Regular follow-up, timely imaging and molecular assessment can help identify drug resistance signals earlier and buy time for subsequent treatment adjustments.

Reference:https://en.wikipedia.org/wiki/Selpercatinib