3661 - Etoposide-Platinum Rechallenge in Small Cell Lung Cancer Worth More Application: A Multicenter Study and an Online Prediction Tool
Presenter(s)
Z. Wei1,2, Y. Liu2, Z. Huang3, X. Z. Luo4, W. Cui5, X. Liu5, M. Yu6, J. Yu7, Y. Chen5, and X. Meng2; 1Cancer Center, Shandong University, Jinan, China, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 3Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China, 4Department of Cardiology, Qilu Hospital of Shandong University, jinan, ??, China, 5Cancer Center, Shandong University, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 6Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Department of Radiation Oncology, Jinan, Shandong, China, 7Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
Purpose/Objective(s): Guidelines generally recommend platinum re-challenge for patients with small cell lung cancer (SCLC) who progress more than 6 months after first-line platinum-based chemotherapy. However, clinical practice indicates therapeutic benefit in patients with a 3-6-month chemotherapy-free interval (CTFI), warranting re-evaluation particularly in the immunotherapy era. This study aims to investigate the efficacy and safety of etoposide plus platinum re-challenge ± immunotherapy in this controversial population to provide evidence filling this clinical gap, and a user-friendly online web was constructed to facilitate personalized prognostic management.
Materials/Methods: This real-world study enrolled SCLC patients from three hospitals (August 2018–May 2025) who progressed 3–6 months after first-line etoposide-platinum (± immunotherapy) treatment. Patients were stratified based on whether they received etoposide-platinum rechallenge after relapse. We systematically evaluated the efficacy and safety. Based on 44 clinical features, this study assessed three machine learning models to generate survival prediction curves. An interactive online platform was established to assist convenient prognostic evaluation for clinicians.
Results: Between 2018 and 2025, we enrolled 313 limited- or extensive-stage SCLC patients who experienced disease progression with a CTFI of 3-6 months; the median follow-up was 26.3 months. Etoposide plus platinum re-challenge (± immunotherapy) improved mOS (15.0 vs 12.1 months; HR=0.57; 95% CI 0.44-0.76; p < 0.001) and mPFS (5.1 vs 3.6 months; HR=0.58; 95% CI 0.52-0.89; p = 0.004). Etoposide plus platinum re-challenge (± immunotherapy) significantly improved ORR compared to other regimens (46.3% vs. 33.6%), especially in patients who achieved a complete or partial response (CR/PR) during first-line (54.2% vs. 34.0%). Notably, survival benefits from the re-challenge regimen were consistently observed across different progression patterns and disease stages. Regardless of first-line immunotherapy exposure, rechallenge plus immunotherapy conferred significant benefits (median OS 18.1 months vs. 14.6 months for other chemo-immunotherapy; 13.0 months for rechallenge without immunotherapy; p = 0.033). Grade =3 adverse events were comparable between cohorts. Finally, a multi-time-point survival prediction model (3 months to 3 years) was developed for the re-challenge cohort (mean AUC = 0.858) to facilitate prognostic assessment and enhanced monitoring, with a web-based visualization tool: http://43.154.9.125:3838/.
Conclusion: As an inexpensive and widely accessible regimen with controllable adverse events, the etoposide-platinum re-challenge (± immunotherapy) in relapsed SCLC with a CTFI of 3–6 months after first-line therapy offers significant clinical benefits and a manageable safety profile.