Retrospective Data Suggest Role for Immunotherapy in Patients with Large-Cell Neuroendocrine Carcinoma

Large-cell neuroendocrine carcinoma of the lung is a rare lung cancer that has features of both small-cell lung carcinoma and non–small-cell lung cancer. There are no large randomized trials that define optimal treatment for either localized or advanced disease.1

Using the National Cancer Database, a clinical oncology database sourced from hospital registry data collected from more than 1500 accredited cancer facilities, researchers evaluated data from patients with stage IV large-cell neuroendocrine carcinoma who were diagnosed between 2014 and 2016, and whose data included at least 30 days of follow-up. Demographic data included age (20-69 vs ≥70 years), sex, race (whites vs others), insurance status (uninsured vs others), setting of care (academic vs others), Charlson-Deyo score (0 or 1 vs 2 or 3), presence of brain metastasis (yes vs no), and liver metastasis (yes vs no).2

Information regarding these patients’ cancer treatments was limited to their first course of therapy, including surgery for primary lesion (yes vs no), radiation (yes vs no), chemotherapy (yes vs no), and immunotherapy (yes vs no). Survival analysis was performed using Kaplan-Meier curves and log-rank tests.

Data were collected for 661 patients, including 37 patients who were treated with immunotherapy. No significant association between use of immunotherapy and demographics was observed, with the exception of use of chemotherapy (P = .0008). Chemotherapy was administered to 92% of patients who received immunotherapy, and 65% of patients who received non-immunotherapy treatments.

Use of immunotherapy was associated with improved overall survival (P = .017). Landmark analysis in the immunotherapy group showed 12-month and 18-month survival of 34% and 29%, respectively. For the non-immunotherapy group, these statistics were 24% and 15%, respectively.

Multivariate analysis demonstrated that female sex, presence of liver metastases, surgery, use of chemotherapy, and use of immunotherapy (hazard ratio, 0.64; P = .016) were significantly correlated with improved survival.

Based on results of this retrospective study using a large cancer database, researchers suggest that use of immunotherapy may improve overall survival for patients with large-cell neuroendocrine carcinoma. They recommend prospective clinical studies for further validation of the benefit of immunotherapy in this rare pulmonary tumor.


  1. Glisson BS, Moran CA. Large-cell neuroendocrine carcinoma: controversies in diagnosis and treatment. J Natl Compr Canc Netw. 2011;9(10):1122‐1129.
  2. Komiya T, Powell E. Role of immunotherapy in stage IV large cell neuroendocrine carcinoma of the lung. J Clin Oncol. 2020;38:suppl (abstract 9060).