Lurbinectedin for small cell lung cancer (SCLC): Response patterns and survival outcomes by line of therapy.

e20128Background: Small cell lung cancer (SCLC) remains a therapeutic challenge with limited treatment options and poor survival outcomes. Lurbinectedin has been approved for the post-platinum setting, but there is a lack of real-world evidence and information related to its optimal sequencing and effectiveness across different lines of therapy. This study aimed to analyze line-dependent outcomes and response patterns of lurbinectedin in SCLC patients. Methods: In this retrospective multi-center analysis, we enrolled 61 SCLC patients treated with lurbinectedin between January 2020 and December 2024, with 56 patients evaluable for analysis. Patient demographics, treatment histories, and outcomes were collected from electronic medical records. Response assessment was performed using RECIST v1.1 criteria. Overall survival, progression-free survival, and treatment duration were analyzed using Kaplan-Meier methodology, with specific attention to outcomes across different lines of therapy. Results: 61 patients were enrolled, 56 evaluable for analysis (31 males [55%], median age 65 years). Lurbinectedin was administered as second-line therapy in 38 patients, third-line in 15, and fourth/fifth-line in 3. Median overall survival was 7.1 months, overall response rate (ORR) was 37.5% across all treatment lines, with notable variations by line of therapy: 42.1% in second line (n=38), 20% in third line (n=15), and 66.7% in fourth/fifth-line (n=3). Median duration of treatment was 4.3 months. The presence of brain metastases (50% of cohort) did not impact the clinical benefit. Prior immunotherapy exposure (68% of patients) was associated with longer treatment duration (4.6 vs 2.3 months, log-rank p=0.13) and better overall survival (8.8 vs 5.8 months, log-rank p=0.06). Treatment was generally well-tolerated, with predominantly hematologic adverse events including anemia (37.5%), thrombocytopenia (32.1%), and neutropenia (14.3%), mostly Grade 1-2, and no Grade 4 toxicities observed. Conclusions: Lurbinectedin demonstrated meaningful clinical activity in second-line therapy for SCLC, while also showing durable responses in heavily pretreated cases. These findings support the consideration of lurbinectedin beyond second-line therapy in selected SCLC patients, though larger prospective studies are needed to validate these response patterns.