Real-World Lurbinectedin Exhibits Safety and Modest Efficacy in ES-SCLC

After a median follow-up of 5.53 months, the ORR among 238 patients was 23.1%, with respective rates of 24.5% and 14.7% among 204 patients treated in the Netherlands Dutch and 34 who were treated in Italy.

Lurbinectedin (Zepzelca) displayed a favorable safety profile and modest efficacy outcomes as a therapy with compassionate use in patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from a multicenter, international study published in the European Journal of Cancer.

After a median follow-up of 5.53 months (IQR, 4.61-11.71), the objective response rate (ORR) among 238 patients was 23.1% (95% CI, 17.8%-28.4%), with respective rates of 24.5% (95% CI, 18.6%-30.4%) and 14.7% (95% CI, 2.7%-23.9%) among patients who were Dutch (n = 204; 85.7%) and Italian (n = 34; 14.3%). The disease control rates (DCRs) were 45.4% (95% CI, 39.1%-51.7%), 48.0% (95% CI, 41.2%-54.9%), and 29.0% (95% CI, 15.1%-47.5%) among the total, Dutch, and Italian cohorts, respectively.

The median duration of response (DOR) across the entire trial population was 2.8 months (95% CI, 2.0-3.5), the median progression-free survival (PFS) was 2.2 months (95% CI, 1.6-2.8), and the median overall survival (OS) was 5.4 months (95% CI, 4.5-6.3). The respective 6-month PFS and OS rates were 12.2% (95% CI, 8.3%-17.0%) and 42.4% (95% CI, 36.1%-49.0%). Dutch patients had a slightly longer median OS of 5.6 months vs 3.6 months in the Italian cohort but a slightly lower median PFS of 1.8 months vs 2.3 months and median DOR of 2.8 months vs 4.6 months.

“Our study provides valuable real-world insights into the effectiveness and safety of lurbinectedin as compassionate use treatment for ES-SCLC, supporting its use with outcomes consistent with those observed in clinical trials and other real-world studies,” lead author Daniela Scattolin, MD, of the Department of Surgery, Oncology, and Gastroenterology at the University of Padova in Padova, Italy, wrote in the publication with study coinvestigators.“However, the outcomes for patients with poor [performance status] at lurbinectedin start, a chemotherapy-free interval [CFI] of less than 90 days, and brain or liver metastases remain suboptimal, and this should be carefully considered when making treatment decisions.”

The prospective study enrolled patients with ES-SCLC who received 3.2 mg/m² of intravenous lurbinectedin every 3 weeks as second-line treatment or later between November 29, 2019, and September 30, 2024. Patients were selected within a named patient program shared between the Erasmus Medical Center of Rotterdam in The Netherlands and the Veneto Institute of Oncology of Padua, Italy.

Among all patients included in the analysis, the median age was 65 years (range, 39-87), and 48.7% of patients were male. A total of 47.0% of patients had formerly smoked, 94.5% had an SCLC-only histology, and 71.0% had extensive-stage disease with metastasis at diagnosis. Furthermore, 66.8% of patients did not receive prophylactic cranial irradiation, 40.7% were treated with 2 prior lines of therapy, and 45.8% of patients had a partial response as best response on the previous anti-cancer therapy.

The median number of prior lines of treatment was 2 (range, 1-7). The most common site of metastasis at extensive-stage diagnosis was liver (35.7%) followed by bone (24.4%). Most patients had a CFI of less than 90 days (84.4%), received 3 lines of lurbinectedin (45.0%), and had an ECOG performance score of 0 to 1 at initiation of treatment (71.0%).

The Dutch and Italian cohorts were generally balanced, with key differences including the proportion of patients who were male (45.6% vs 67.6%), currently smoking (26.5% vs 41.2%), had receipt of 1 prior line of therapy (29.4% vs 52.9%), and had receipt of prior chemoimmunotherapy (12.3% vs 64.7%).

The primary end points of the study were real-world efficacy, including ORR, DCR, DOR, PFS, and OS, and safety. Secondary end points included patient clinical-pathological characteristics and treatment management.

A multivariate Cox-regression analysis revealed particular benefit among patients with a CFI of 90 days or greater vs those with chemotherapy-resistant disease; the median PFS was 3.1 months vs 1.8 months, respectively (HR, 0.46; 95% CI, 0.30-0.71; P <.001), and the median OS was 6.8 months vs 4.5 months (HR, 0.56; 95% CI, 0.37-0.85; P = .006).

Treatment-related adverse effects (TRAEs) were observed in 92% of patients, with 29% of patients experiencing at least 1 grade 3 or 4 TRAE. The most common AEs included fatigue (46%), anemia (38%), neutropenia (35%), increased gamma-glutamyl transferase levels (24%), aspartate transferase or alanine aminotransferase increases (22%), thrombocytopenia (21%), nausea (20%), and hypoalbuminemia (19%).

Reference

Scattolin D, Dingemans AMC, Dal Maso A, et al. Outcome and safety of lurbinectedin as compassionate use in extensive stage small cell lung cancer: a multicentric international cohort. Eur J Cancer. Published online July 2, 2025. doi:10.1016/j.ejca.2025.115595