Will there be resistance issues with evantuzumab?

Although evantumumab (amivantamab), a bispecific antibody targeting EGFR and MET, has shown significant efficacy in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), drug resistance is still a concern. According to overseas research and clinical observations, patients may experience tumor progression again after receiving evantumumab for a period of time, suggesting that it is not permanently effective and that the development of resistance mechanisms is more complicated in some cases.

The formation of drug resistance may involve multiple mechanisms, includingremodeling of downstream signaling pathways of EGFR and MET, activation of other bypass pathways, changes in the tumor microenvironment, or changes in the expression of cell surface receptors. For example, new gene mutations such as KRAS, PIK3CA or EGFR C797S may be observed in some patients. These mutations can bypass the originally blocked signaling pathways, thus causing drug failure. In addition, tumor cells may also form alternative growth signals by increasing MET expression or activating receptors such as HER3, which weakens the targeting effect of evantumumab.

In terms of response strategies, researchers are exploring the combination of other targeted drugs, immunotherapy or chemotherapy to delay or overcome the occurrence of drug resistance. For example, combining evantumumab with EGFR-TKIs such as Lazertinib has shown the potential to extend the duration of efficacy. In the future, with in-depth research on the mechanisms of drug resistance, the optimization of individualized treatment plans is expected to improve the long-term effects of this type of targeted therapy. Although the problem of drug resistance cannot be ignored, it does not mean that treatment is ineffective, but it prompts the need to continuously adjust strategies and find more precise treatment paths.

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