Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When KI‐67 is ≥10%?

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%. Implications for practice The results of the study call in the question the anti-proliferative activity of SSAs in panNETs with Ki-67 ≥10%. Patients with G2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results, in order to optimize tailored therapeutic strategies for this specific patient population. This article is protected by copyright. All rights reserved.