GEP Neuroendocrine Tumors: Systemic Therapy

GEP Neuroendocrine Tumors: overview

This algorithm addresses systemic therapy for gastroenteropancreatic (GEP) neuroendocrine neoplasms, and the first branch point is differentiation. For well-differentiated neuroendocrine tumors that are somatostatin receptor positive (SSTR+), the first-line options are a somatostatin analog for antiproliferative control, supported by CLARINET, and peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, supported by NETTER-1. Poorly differentiated, high-grade neuroendocrine carcinoma is treated as a small-cell-like disease with platinum plus etoposide.

For tumors that progress after a somatostatin analog, the second-line branch lists everolimus, an mTOR inhibitor (RADIANT-4), and two options shown specifically for pancreatic NET: the tyrosine kinase inhibitor sunitinib, and capecitabine plus temozolomide (CAPTEM). The chart therefore separates receptor-positive, well-differentiated disease, where SSTR-directed therapy comes first, from high-grade carcinoma, where platinum-based chemotherapy is the backbone.

Trials behind this algorithm

• CLARINET trial, lancreotide vs pbo Caplin et al, NEJM, 2014, PMID: 25014687
• NETTER-1 Trial Strosberg et al, NEJM, 2017, 28076709

Background reading: Neuroendocrine tumors (NETs) board review notes.