Efficacy of immune checkpoint inhibitors in advanced large cell neuroendocrine carcinoma of the lung: A single-institution experience

Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly invasive lung cancer subtype with an overall poor prognosis. Due to its low incidence rate and unusual pathological features, the clinical management of LCNEC remains controversial. The present study aimed to assess the effect of immune checkpoint inhibitors (ICIs) on treatment response and survival outcomes in patients with advanced LCNEC. The clinical data from 148 patients with LCNEC treated with ICIs at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2019 and September 2021 were retrospectively analyzed. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate associations between clinicopathological variables and patient outcomes. Patients treated with ICIs demonstrated extended median overall survival (mOS) times [23.5 months; 95% confidence interval (CI), 18.524-28.476] compared with patients who did not receive ICIs (11.2 months; 95% CI, 4.530-18.930) (P<0.001). Univariate analysis revealed that histological subtype (P=0.043), lymph node metastases (P=0.032) and number of metastatic organs (P=0.009) were associated with a poor prognosis. The heterogeneity of pathological components was associated with prognosis, and the mOS time was shorter for mixed LCNEC than that for pure LCNEC (P=0.043). The median progression-free survival (mPFS) (9.78 vs. 9.37 months; P=0.82) and mOS (20.70 vs. 25.79 months; P=0.181) times showed no significant association with regard to different regimens of immuno-based combination therapy (chemotherapy combined with ICIs vs. anti-angiogenic agents combined with ICIs). Poor Eastern Cooperative Oncology Group performance status score (P=0.04), multiple organ metastases (P=0.02) and high cancer antigen 125 levels (P=0.01) were independent risk factors of a poor prognosis. The present findings offer valuable insights into potential prognostic markers and highlight the favorable impact of ICIs on OS in advanced LCNEC. Prospective clinical studies are required to validate the therapeutic value of ICIs in LCNEC.