Systematic review and meta-analysis of efficacy and safety of immunotherapy in advanced pulmonary large-cell neuroendocrine carcinoma

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an aggressive malignancy with limited treatment options. Management often follows small cell lung cancer regimens; however, the benefit of immune checkpoint inhibitors (ICIs) is uncertain due to a lack of randomized trials. A systematic review and meta-analysis evaluated the clinical impact of ICI-containing regimens in advanced LCNEC. In the literature through 2025, the author identified 22 eligible studies involving 3537 patients. The pooled objective response rate (ORR) for chemotherapy (chemo) plus ICI was 49% (95% CI 43-55). Compared with chemo alone, chemo plus ICI significantly improved ORR (OR 2.52; 95% CI 1.59-4.02). The pooled median progression-free survival with chemo plus ICI was 7.4 months, with a significant benefit versus chemo alone (HR 0.51; 95% CI 0.39-0.67). In the first-line setting, chemo plus ICI improved overall survival versus chemo alone (HR 0.72; 95% CI 0.58-0.89). The incidence of grade ≥ 3 adverse events did not significantly differ between chemo plus ICI and chemo alone. The authors conclude that in this analysis, chemo plus ICI improved clinical outcomes over chemo alone in patients with advanced LCNEC. Confirmation in prospective trials is warranted.