Real-world Outcomes of Immune Checkpoint Inhibitors as Second-line Therapy for Extensive-stage Small-cell Lung Cancer: A Multicenter Retrospective Analysis

Jiao Zhang¹Jia-Xing Guo²Ping Li^3,4Xiaoye Jin⁵Yan Wang^6*Lujun Zhao^7*

• ¹The Third Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, China, Yinchuan, China
• ²Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot010000, Inner Mongolia Autonomous Region, China;, Hohho, China
• ³General Hospital of Ningxia Medical University Department of Pharmacy, Yinchuan, China
• ⁴Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan750004, Ningxia, China;, Yinchuan, China
• ⁵College of Clinical Medical, Ningxia Medical University, Yinchuan750004, Ningxia, China;, Yinchuan, China
• ⁶The Third Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan750004, Ningxia, China;, Yinchuan, China
• ⁷Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin300060, China;, Tianjin, China

Background: There is limited evidence concerning real-world evidence of second-line (2L) treatment with immune checkpoint inhibitors (ICIs) in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we evaluated the efficacy of 2L-ICIs therapy in patients with ES-SCLC. Methods: In this retrospective study, we included patients with ES-SCLC who experienced disease progression following first-line (1L) therapy and received 2L treatment between March 2019 and December 2023. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints included safety, the objective response rate (ORR), the disease control rate (DCR), and overall survival (OS). Survival analyses were conducted using Kaplan-Meier curves. One-to-one propensity score matching (PSM) was used to reduce confounding. Univariate and multivariate Cox regression analyses were conducted to identify factors associated with PFS and OS. Results: We included 496 patients in this study; among them, 200 patients were in the 2L-ICIs group and 296 patients were in the 2L-non-ICIs group. The 2L-ICIs group demonstrated significantly longer PFS than the 2L-non-ICIs group (median PFS: 4.13 vs. 2.70 months; p < 0.001), and this benefit persisted after PSM (median PFS: 4.21 vs. 2.87 months; p < 0.001). The 2L-ICIs group also had a significantly higher ORR (ORR: 29.5% vs. 10.1%; p < 0.001) and DCR (DCR: 67.0% vs. 51.7%; p < 0.001). Treatment-related adverse events were comparable between the groups, with only one grade 3 rash reported in the 2L-ICIs group. Multivariate Cox regression identified liver metastases, the number of metastatic lesions, and the 1L-PFS as independent predictive factors for PFS. Conclusion: In this study, 2L-ICIs demonstrate significant clinical benefits with acceptable toxicity in ES-SCLC patients who progressed after 1L therapy, supporting their use as a clinically actionable option.