Antibody-conjugated drug combination treatment for Osimertinib (Tagrisso) resistance cases

Antibody drug conjugate (ADC) combined with osimertinib for the treatment of drug-resistant lung cancer has gradually attracted attention in clinical studies and real cases in recent years, especially for the emergence of EGFR-TKIPatients with third-generation drug resistance, MET amplification, HER3 high expression or EGFR rare mutations. Some cases have shown that when patients develop disease progression after taking osimertinib for about a year, combined treatment with HER3-ADC (such as Patritumab deruxtecan) or MET-ADC can regain tumor control in the short term, shrink the tumor or delay further deterioration. The basis for this type of combination strategy mainly comes from the remodeling of tumor cell signaling pathways after drug resistance, making them more susceptible to being targeted by ADCs and releasing cytotoxic payloads.

In a representative case, the patient was confirmed to have HER3 high expression and MET mild amplification due to the enlargement of the chest lesions after taking osimertinib for 18 months, and was subsequently treated with HER3-ADC combined with osimertinib. Significant tumor shrinkage can be observed within about 6 weeks of imaging follow-up, and symptoms such as cough and chest tightness are also significantly improved. The treatment logic of this type of combination is to use osimertinib to continue to inhibit the main pathway of EGFR, while at the same time the ADC directly delivers cytotoxic drugs into the tumor to form a double killing, thereby achieving objective relief again in the drug-resistant stage.

However, not all patients are suitable for the "osimertinib +ADC" model. Some cases suggest that if the resistance mechanism is driven by small cell transformation or KRAS mutation, the effect of combining ADC is relatively limited. In addition, because the ADC drug itself may cause side effects such as neutropenia, nausea, fatigue, and interstitial pneumonia, some patients need to adjust the dose or temporarily discontinue the drug due to adverse reactions during treatment. Therefore, gene testing, protein expression evaluation, and overall tolerability evaluation must be performed before combination therapy to determine whether there is a basis for benefit.

In general, antibody conjugated drugs combined with osimertinib are currently the most effective method for EGFR late-stage mutationNSCLCAn important exploration direction after drug resistance, it can bring new remission opportunities in specific groups, especially suitable for cases with high expression of HER3 , MET amplification or multiple bypass activation leading to drug resistance. However, this strategy is still a relatively cutting-edge precision treatment plan. Patients need to undergo molecular testing, efficacy monitoring and adverse reaction management under the guidance of a professional oncology team to maximize benefits and ensure safety.

Reference:https://reference.medscape.com/

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