Outcomes of Chemoimmunotherapy in Metastatic Pancreatic Neuroendocrine Carcinoma: A Single-Center Clinicopathologic Study

BACKGROUND: Pancreatic neuroendocrine carcinomas (PanNECs) are a rare, aggressive subtype of pancreatic neuroendocrine neoplasms. Based upon similarities to small cell lung cancer (SCLC), advanced PanNECs are commonly treated with platinum and etoposide chemotherapy; however, outcomes remain poor. Although first-line chemoimmunotherapy has improved survival in SCLC, its role in PanNEC is not well defined. METHODS: We report on a retrospective cohort of 13 patients with metastatic PanNEC treated at Memorial Sloan Kettering with either first-line combined chemoimmunotherapy or first-line chemotherapy alone. RESULTS: In the first-line metastatic setting, patients who received chemoimmunotherapy (N = 5) demonstrated longer median progression-free survival (17.0 months vs. 2.8 months, P = 0.002) and overall survival (31.0 months vs. 16.0 months, P = 0.031) compared with those who received chemotherapy alone (N = 8). In the second line or later setting, five patients received immunotherapy-containing regimens with a median progression free survival of only 3.0 months (95% confidence interval 1.4 months, Not Reached). Radiologic responses observed in patients receiving chemoimmunotherapy in the first-line metastatic setting were 2 complete responses and 3 partial responses. Germline variants included one patient with a BRCA2 mutation, one patient with co-existing BRCA2 and ATM mutations, and one patient with a MUTYH mutation. Exploratory genomic analyses showed common mutations in TP53, RB1, and KRAS, low tumor mutational burden, and microsatellite stability. Exploratory multiplex immunofluorescence demonstrated heterogenous immune cell infiltrates without a consistent biomarker pattern associated with response. CONCLUSION: In this single-center cohort, early incorporation of chemoimmunotherapy in PanNEC was associated with improved survival. These findings are hypothesis-generating and support prospective, multicenter evaluation of first-line chemoimmunotherapy strategies in PanNEC (SWOG S2012, NCT05058651) [1].