Second-line therapy in extensive-stage small cell lung cancer: an unmet need highlighted by real-world evidence from the LALUCA registry

Background Extensive-stage small cell lung cancer (ES-SCLC) has a dismal prognosis as patients progress within months after first-line systemic treatment. Until recently, topotecan was the only approved second-line treatment in Europe. However, due to its limited efficacy, various treatment strategies are being employed. This study aimed to depict the therapeutic landscape of second-line treatment in ES-SCLC and to evaluate survival outcomes in a real-world setting.Methods Data from the Austrian LALUCA registry, a prospective, multicenter clinical lung cancer registry, were reviewed for all patients diagnosed with ES-SCLC between November 2020 and October 2025. Clinical and treatment characteristics were assessed with special emphasis to second-line treatment. The primary outcomes were overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT).Results Among 203 patients with histologically confirmed ES-SCLC included in this study, 75 patients (36.9%) received second-line therapy. The main reason for no second-line treatment (n = 128) at data cut-off was death in 49.2% and switch to best supportive care in 18.8%. Second-line treatment consisted of anthracycline-based treatment regimens in 57.3%, topotecan in 26.7% and re-challenge of platinum-based chemo- or chemoimmunotherapy in 16.0% of patients. The median duration of second-line treatment was 2 months (range: 0.0-8.2) with a median PFS of 4.7 months (95% CI: 3.9, 5.8), and median OS of 7.1 months (95% CI: 5.1, 9.3). The median TTNT between first- and second-line treatment was 6.4 months (range: 0.3 - 38.7). The main reasons for treatment discontinuation were disease progression in 30.7%, followed by completed regimen in 24.0% and death in 13.3%.Conclusion This real-world analysis shows poor outcomes in patients with progressing ES-SCLC, reflected by both short median PFS and duration of second-line treatment, along with high rates of treatment discontinuation due to progression, highlighting the urgent need for more effective and tolerable treatment options.