Immune Checkpoint Inhibitors Continuation Beyond Progression as Second-Line Treatment for Extensive-Stage Small-Cell Lung Cancer: A Real-World, Multicenter Analysis

Jiao Zhang¹Rui Zi²Haixia Zhang¹Ye Lv¹Lujun Zhao^3*Yan Wang^1*

• ¹The Third Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, China, Yinchuan, China
• ²The First Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan750004, Ningxia, China, Yinchuan, China
• ³Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin300060, China, Tianjin, China

Background: Optimal management of extensive-stage small-cell lung cancer (ES-SCLC) following progression on first-line (1L) chemoimmunotherapy remains undefined. This study aimed to evaluate the efficacy of immune checkpoint inhibitors (ICIs) continuation in a second-line (2L) treatment setting. Methods: A total of 211 ES-SCLC patients with disease progression after 1L chemoimmunotherapy were analyzed retrospectively after stratifying them into ICIs continuation (n = 118) and ICIs discontinuation (n = 93) cohorts. The primary endpoint was 2L overall survival (2L-OS), and the secondary endpoints included 2L progression-free survival (2L-PFS), objective response rate (2L-ORR), disease control rate (2L-DCR), and safety. Propensity score matching (PSM, 1:1) ensured balanced baseline characteristics. Survival analyses were conducted based on Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to identify the factors associated with 2L-PFS and 2L-OS. Results: ICIs continuation significantly improved 2L-OS (8.66 vs 7.90 months; P = 0.016) and 2L-PFS (3.92 vs. 2.15 months; P < 0.001). The benefits of ICIs continuation persisted after PSM (2L-OS: 8.9010.31 vs. 7.808.95 months, P = 0.0450.027; 2L-PFS: 3.824.22 vs. 2.202.12 months, P < 0.001). In addition, the ICIs continuation group demonstrated superior tumor response (2L-ORR: 28.8% vs. 11.8%, P = 0.003; 2L-DCR: 65.3% vs. 44.1%, P = 0.002), which remained significant post-PSM. Treatment-related adverse events (AEs) were comparable between the groups, while immune-related AEs were predominantly low grade in the ICIs continuation group. Multivariate analysis revealed that baseline liver metastasis and 1L-PFS were independent risk factors for 2L-PFS and 2L-OS, whereas overweight (BMI 25.0-29.9) was an independent prognostic factor for 2L-OS.Multivariate analysis revealed baseline liver metastasis and 1L-PFS as independent risk factors for 2L outcomes. The exploratory analysis conducted for the ICIs continuation cohort revealed no significant difference in patient survival between the continuing ICIs treatment group and switching ICIs treatment group (2L-OS: P = 0.668; 2L-PFS: P = 0.346). Conclusion: In patients with ES-SCLC who exhibit disease progression after 1L chemoimmunotherapy, continuation of ICIs significantly improves survival and tumor response while achieving a manageable safety profile. Therefore, ICIs continuation may be considered a viable strategy in 2L settings.