HER2-Mutated NSCLC: Testing and Emerging Treatment Approaches - Episode 3
Antibody-Drug Conjugate Efficacy and Safety in HER2-Mutated NSCLC
Panelists discuss how antibody drug conjugates like trastuzumab deruxtecan work as “Trojan horses” to deliver chemotherapy directly to tumor cells, providing effective second-line treatment for patients with HER2-mutated disease but requiring careful management of chemotherapy-like adverse effects, including significant toxicities.
Video content above is prompted by the following:
Antibody drug conjugates (ADCs) represent a revolutionary approach for HER2-mutated non–small cel lung cancer (NSCLC) treatment, with trastuzumab deruxtecan (T-DXd) approved in the second-line setting. Dr Preeshagul explains ADCs using the “Trojan horse” analogy, where a friendly-appearing antibody delivers chemotherapy directly to tumor cells expressing HER2. This targeted delivery system allows for more precise treatment of HER2-positive cancers while theoretically reducing systemic chemotherapy exposure.
T-DXd demonstrates significant efficacy in patients with HER2-mutated NSCLC, but it comes with substantial chemotherapy-like toxicities including neutropenia, fatigue, nausea, and diarrhea. Unlike traditional targeted therapies such as EGFR inhibitors, ADCs retain chemotherapy components that cause familiar adverse effects. The drug is approved for both HER2 mutations and HER2 amplification (immunohistochemistry 2+ and 3+ expression levels) in the second-line setting, expanding treatment options for different HER2 alteration subtypes.
Managing ADC-related toxicities requires comprehensive supportive care and careful patient monitoring. The chemotherapy component of these conjugated antibodies means patients experience similar adverse effects to traditional chemotherapy regimens. Oncologists must balance the significant efficacy benefits against tolerability challenges, particularly in patients who may have received prior platinum-based chemotherapy. Proper patient selection and toxicity management are crucial for optimizing outcomes with ADC therapy.
Related Content:
