Real World Outcomes With Chemotherapy and Immunotherapy in Metastatic Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinomas

BACKGROUND: Gastroenteropancreatic poorly differentiated neuroendocrine carcinomas (GEP-NECs) are aggressive cancers where cytotoxic chemotherapy is the backbone of treatment. While the addition of immunotherapy with immune checkpoint inhibitors (IOs) to chemotherapy is recommended for lung NECs, evidence regarding IO efficacy in GEP-NECs is limited. We explore outcomes with systemic therapies in patients with metastatic GEP-NECs using the National Cancer Database (NCDB). METHODS: Cases of metastatic GEP-NECs with years of diagnosis between 2018 and 2022 were identified within the NCDB. Overall survival (OS) was analyzed using Kaplan-Meier estimations and Cox proportional hazards regression. RESULTS: Four thousand one hundred twenty-seven cases were included. 1209 (29.29%) patients did not receive any systemic therapy (chemotherapy/immunotherapy/both). Among the 2918 patients that received systemic therapy, 758 (25.98%) patients received immunotherapy (immunotherapy alone = 21; chemotherapy plus immunotherapy [chemoIO] = 737). The percentage of patients receiving immunotherapy alongside chemotherapy increased from 12.27% in 2018 to 34.18% in 2022. Two thousand two hundred eighty cases were included for survival analysis. Patients treated with chemoIO (N = 532) had prolonged OS versus chemotherapy alone (N = 1748), with median OS of 10.51 months vs. 8.31 months (HR, 0.77; 95% CI, 0.69-0.85; p < 0.001). The association was significant in all histological subgroups (small-cell, p < 0.001; large-cell, p = 0.04; others/not specified, p = 0.01). CONCLUSIONS: Combination chemoIO may improve survival in metastatic GEP-NECs as compared to chemotherapy alone. Results of currently ongoing clinical trials exploring the role of immunotherapy in extrapulmonary NECs may help guide clinical practice in GEP-NECs.