Immune checkpoint inhibitors combined with anti-angiogenic therapy as second- or further-line treatment for small cell lung cancer: Efficacy, safety, and prognostic biomarkers.

Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options, especially after failure of initial therapy. Immune checkpoint inhibitors (ICIs) and anti-angiogenic agents have emerged as promising options for relapsed SCLC. This observational study aimed to evaluate the effectiveness and safety of ICIs plus anti-angiogenic therapy for relapsed SCLC patients, and to identify potential prognostic indicators. A single-center cohort of SCLC patients treated with ICIs plus anti-angiogenic therapy or anti-angiogenic monotherapy after first-line treatment was established. Efficacy and safety were compared between the two treatment modalities. The endpoints included progression-free survival (PFS), overall survival, disease control rate (DCR), objective response rate, and adverse events (AEs). Prognostic biomarkers, including clinicopathological parameters, plasma proteomics, and extracellular vesicle (EV) membrane proteins, were evaluated using blood samples taken before and after two cycles of combination therapy. The observation and control groups comprised 40 and 21 patients. Baseline information was comparable. Combination therapy significantly improved PFS (4.0 vs. 2.7 months, p = .029) and DCR (77.5% vs. 52.4%, p = .044). Safety profiles were comparable between groups, with low rates of severe AEs. Four clinicopathological factors (liver metastases, baseline NSE levels, smoking history, and sex) and eight plasma proteins were associated with PFS and therapy response. EV membrane protein interleukin-12 was identified as a promising poor-prognosis biomarker. ICIs plus anti-angiogenic therapy showed promising efficacy and safety for relapsed SCLC, outperforming anti-angiogenic monotherapy. Clinicopathological factors and blood-based biomarkers have shown potential to predict PFS and response to combination treatment.