How would you treat a widely metastatic poorly differentiated pancreatic neuroendocrine cancer?

The standard first line systemic therapy for poorly differentiated extrapulmonary neuroendocrine carcinoma (EP NEC) remains PE or platinum and etoposide (with some studies suggesting superiority of cis over carbo which likely reflects bias from patient characteristics). This is based on less than optimal data, much of it quite dated.

When PE is used, I typically treat for 4-6 cycles and then stop. SWOG has a trial for EP NECs looking at the potential role of adding immunotherapy to PE (SWOG S2012...

Tumor grade matters a great deal in pancreatic neuroendocrine tumors (PNET). When you are treating poorly differentiated, as opposed to well-differentiated or even moderately-differentiated, disease -- and especially when dealing with widely metastatic/high-volume situations -- I strongly favor starting with cytotoxic therapy rather than a targeted agent such as everolimus or sunitinib. This typically consists of a platinum/etoposide combination, similar to small cell lung cancer regimens; howev...