BACKGROUND

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 study analysis, we enrolled SCLC patients treated with lurbinectedin between January 2020 and December 2024. 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

A total of 64 patients were enrolled, with 59 evaluable for analysis (36 males [56.3 %], median age 65 years [range 37-81]). Lurbinectedin was given as second-line therapy in 39 patients (66.1 %) and as third-line or beyond in 20 patients (33.9 %). The overall response rate (ORR) was 37.3 % (n = 22), including 1 complete response (1.7 %) and 21 partial responses (35.6 %). By line of therapy, the ORR was 38.5 % (n = 15) in second-line and 35.0 % (n = 7) in third-line or later. The median overall survival (mOS) for all evaluable patients was 7.7 months, and the median duration of treatment (mDoT) was 4.3 months. At data cutoff, 13 patients (22 %) were alive and censored in the OS analysis, with a median follow-up of 8.5 months among survivors. Prior immune checkpoint inhibitor (IO) exposure was documented in 71.9 % of patients (n = 46); although those with prior IO had numerically longer mOS (8.8 vs. 6.0 months, p = 0.06) and mDoT (4.6 vs. 2.3 months, p = 0.14), neither difference reached statistical significance. This survival analysis included 43 patients in the prior-IO group (3 patients with prior IO were excluded due to incomplete follow-up) and 16 patients in the no-IO group. The presence of baseline brain metastases (47 %) did not preclude clinical benefit. Treatment was generally well tolerated: the most common hematologic toxicities observed were anemia (44.1 %), thrombocytopenia (37.3 %), and neutropenia (15.3 %), predominantly grade 1-2, and no grade 4 adverse events were 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 also beyond second-line therapy in selected SCLC patients, though larger prospective studies are needed to validate these response patterns.