Abstract
BACKGROUND: Large-cell neuroendocrine carcinoma of the lung (LCNEC) shares clinicopathological features with both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Owing to its neuroendocrine characteristics, the treatment of LCNEC often follows paradigms established for SCLC. Immune checkpoint inhibitors (ICIs) have become the standard first-line therapy for extensive-stage SCLC (ES-SCLC), but evidence supporting the use of ICIs in advanced LCNEC remains limited. This study aimed to evaluate the efficacy and prognosis of first-line ICIs in patients with advanced LCNEC. METHODS: We retrospectively analyzed 31 patients with stage IV LCNEC treated at Inner Mongolia People's Hospital from January 2019 to December 2024. Of these, 14 patients received ICIs plus platinum-based chemotherapy (the ICIs + Chemo group), and the other 17 patients received chemotherapy alone (the Chemo group). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events(AEs) were compared between the two groups. RESULTS: After a median follow-up of 24 months, the ICIs + Chemo group demonstrated significantly longer median PFS (10.5 months [95% CI, 7.6-12.4] vs. 6.0 months [95% CI, 4.3-7.7]; p=0.035) and median OS (15.0 months [95% CI, 11.4-18.6] vs. 11.0 months [95% CI, 9.3-12.6]; p=0.036) compared to the Chemo group. Multivariate Cox regression showed that the ICIs + Chemo group reduced the risk of progression by 49% (HR = 0.51; 95% CI, 0.28-0.92; p=0.026) and death by 45% (HR = 0.55; 95% CI, 0.30-1.01; p=0.054). The ORR and DCR were 50.0% and 85.7% in the ICIs + Chemo group, versus 29.4% and 76.5% in the Chemo group, respectively. Immune-related adverse events (irAEs) in the ICIs + Chemo group were grade 1-2, with no grade 3 or higher adverse events observed. CONCLUSION: This study was based on real-world data from northern China. Preliminary findings suggest that ICIs combined with chemotherapy may be a promising treatment option for patients with advanced LCNEC, with potential survival benefits. However, as a single-center retrospective study with a limited sample size, further multi-center and large-sample prospective clinical trials are warranted to validate these results.