Somatostatin analogs for pancreatic neuroendocrine tumors: any benefit when KI-67 is ≥10%?

Abstract

Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. Materials and methods: To assess the clinical outcomes of advanced, non-functioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multi-center study including patients treated between 2014-2018 across ten centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), while overall survival (OS) and treatment safety were secondary endpoints. Results: 73 patients were included (68 G2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173 months), the median TNT and PFS were 14.2 months (95% CI, 11.6-16.2 months) and 11.9 months (95% CI, 8.6-14.1 months) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs lanreotide), while increased tumor grade (HR: 4.4, 95% CI, 1.2-16.6; p=0.04) and hepatic tumor load (HR: 2, 95% CI, 1-4; p=0.03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR: 3.4, 95% CI, 1.2-10; p=0.01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. Conclusions: SSAs exert antiproliferative activity in PanNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%.