Outcomes of Lurbinectedin in Central Nervous System Metastases of Small Cell Lung Cancer: A Single-Institution Retrospective Case Series

Background/Objectives: Central nervous system (CNS) metastases are a frequent and morbid complication of small cell lung cancer (SCLC), with limited effective systemic treatment options. Lurbinectedin has demonstrated systemic activity in relapsed SCLC; however, its intracranial efficacy remains unclear because patients with active CNS disease were underrepresented in pivotal trials. We evaluated real-world intracranial outcomes of lurbinectedin in patients with SCLC and CNS metastases. Methods: A single-institution retrospective case series was conducted among adult patients with histologically confirmed SCLC and radiologic CNS metastases treated with lurbinectedin between July 2020 and April 2025. Primary endpoints were CNS disease control rate (CNS-DCR), defined as radiographic stability or improvement lasting ≥8 weeks, and intracranial progression-free survival (iPFS), defined as time from lurbinectedin initiation to clinical or radiographic CNS progression or death. Results: Thirty patients received lurbinectedin; 14 (46.7%) had CNS metastases at any time. Five patients (16.7%) had baseline CNS metastases prior to lurbinectedin initiation, while nine (30.0%) developed CNS metastases during treatment. Among patients with baseline CNS disease, one patient demonstrated radiographic intracranial improvement at approximately 4 months; however, systemic progression at 5 months limited further assessment of response duration. The remaining four patients experienced intracranial progression within 2–4 months. One of five patients with baseline CNS metastases met the predefined CNS disease control endpoint; this descriptive proportion corresponds to 20% within our small sample. Median iPFS was approximately 2.5 months. No CNS-specific adverse events attributable to lurbinectedin were observed. Conclusions: In this single-institution retrospective case series, limited intracranial disease control was observed among SCLC patients with baseline CNS metastases treated with lurbinectedin. Given the small number of evaluable patients, these findings should be interpreted as descriptive and hypothesis-generating rather than a conclusive efficacy analysis. Prospective studies incorporating CNS-specific endpoints are needed to better define the role of lurbinectedin and other systemic therapies in intracranial disease management.