Real-World Outcomes of Sevabertinib in HER2-Mutant Advanced NSCLC: A Bidirectional Cohort Study

This is a single-center, observational, bidirectional cohort study evaluating the real-world effectiveness, safety, and quality of life associated with sevabertinib in Chinese adults with HER2-mutant advanced non-small cell lung cancer receiving sevabertinib as second-line or later-line therapy. The study will include both retrospectively identified patients and prospectively enrolled patients. The primary objective is to evaluate real-world progression-free survival. Additional assessments include tumor response, overall survival, safety, and patient-reported quality of life.

Inclusion Criteria: 1. Age ≥18 years at the index date. 2. Unresectable locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). 3. Documented HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutation. 4. Received at least one prior systemic therapy for advanced NSCLC. Prior HER2-targeted antibody-drug conjugate (ADC) therapy is permitted, whereas prior HER2-targeted tyrosine kinase inhibitor (TKI) therapy is not permitted. 5. For retrospectively included participants, sufficient baseline clinical, treatment, and prior follow-up data are available. 6. Sevabertinib treatment has been determined by the treating physician based on clinical practice, or the participant has already initiated sevabertinib at screening. Exclusion Criteria: 1. History of Grade 3 or higher interstitial lung disease (ILD), or evidence of any clinically active ILD. 2. Uncontrolled comorbid diseases or conditions, including but not limited to decompensated respiratory, cardiac, hepatic, or renal disease; ongoing or active infection, including active clinical tuberculosis; renal transplantation; or psychiatric/social conditions that may limit study compliance. 3. Unstable brain metastases. 4. Inability to comply with the study for any reason. 5. Receipt of another unapproved investigational drug or non-drug treatment within 30 days before the index date or during the observation period.