HER2-Mutated NSCLC: Testing and Emerging Treatment Approaches - Episode 2
Panelists discuss how patients with HER2-mutated lung cancer represent a high-risk population with aggressive biology and propensity for brain metastases, currently treated with standard chemotherapy in the frontline setting while awaiting clinical trials that may move HER2-targeted agents to first-line treatment.
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Patients with HER2-mutated non–small cel lung cancer (NSCLC) present with aggressive disease characteristics, including high propensity for brain metastases and challenging clinical features. Joshua Sabari, MD,notes these patients are often younger, never-smokers with high-risk disease biology similar to other oncogenic drivers. Currently, frontline treatment remains standard chemotherapy with carboplatin and pemetrexed, with or without immunotherapy, as no HER2-targeted agents are approved for first-line therapy in lung cancer.
Brain metastases management in HER2-mutated NSCLC requires careful consideration due to the high incidence of central nervous system (CNS) involvement. Both experts recommend upfront radiation therapy for patients with active brain metastases, as standard chemotherapy and immunotherapy combinations lack adequate CNS penetration. The decision for radiation depends on factors including number of brain lesions, size, presence of edema, and overall disease burden. Early CNS-directed therapy is preferred until better brain-penetrating systemic therapies become available.
Clinical trial enrollment represents a critical opportunity for patients with newly diagnosed HER2-mutated NSCLC, as several studies are evaluating HER2-targeted agents in the frontline setting. These trials compare standard carboplatin-based chemotherapy with novel HER2-directed therapies, potentially moving targeted treatments earlier in the treatment sequence. Patient participation in clinical trials is essential for advancing the field and potentially accessing more effective treatments before they receive regulatory approval.