As antibody-drug conjugates reshape the oncology landscape, a critical gap remains between clinical trial populations and the patients actually receiving these therapies in routine practice. For Chinese adults living with HER2-mutant metastatic non-small cell lung cancer — a molecularly defined subgroup historically underserved by targeted options — how trastuzumab deruxtecan performs outside controlled trial conditions carries real consequence for treatment planning and survival expectations.
The RERUN study is a prospective, multicenter observational cohort enrolling approximately 150 Chinese adults across roughly 30 clinical sites. All participants carry pathologically confirmed activating HER2 mutations in unresectable or metastatic non-squamous NSCLC and are receiving trastuzumab deruxtecan (T-DXd) as second-line or later therapy. The primary endpoint is investigator-assessed real-world progression-free survival, with the follow-up period designed to capture approximately 60% event maturity — a threshold chosen to ensure statistically meaningful PFS estimates. Secondary outcomes encompass time to treatment discontinuation, overall survival, and safety signals in this ethnic subgroup.
This protocol publication describes study design rather than results, so no efficacy data are yet available. That said, the study's significance lies in what it addresses structurally. T-DXd achieved regulatory approval in China based substantially on data from the global DESTINY-Lung trials, which enrolled limited numbers of East Asian patients. Pharmacokinetic differences, comorbidity patterns, and prior treatment histories in Chinese clinical practice may diverge meaningfully from the pivotal trial population. Real-world observational data, while unable to establish causality or control for confounders the way a randomized trial can, routinely capture heterogeneous patients excluded from registration studies — those with brain metastases, reduced performance status, or complex prior therapy histories. For a drug class where interstitial lung disease represents a significant and sometimes fatal adverse event, safety surveillance in a real-world Chinese cohort carries added urgency. The RERUN dataset, once mature, should help clinicians contextualize trial-derived benefit estimates against the messier realities of everyday oncology practice.