Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

Elettra Merola, Teresa Alonso Gordoa, Panpan Zhang, Taymeyah Al-Toubah, Eleonora Pellè, Agnieszka Kolasińska-Ćwikła, Wouter Zandee, Faidon Laskaratos, Louis de Mestier, Angela Lamarca, Jorge Hernando, Jaroslaw Cwikla, Jonathan Strosberg, Wouter de Herder, Martin Caplin, Mauro Cives*, Rachel van Leeuwaarde

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


BACKGROUND: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (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, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints.

RESULTS: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .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 = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea.

CONCLUSION: 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 into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.

Original languageEnglish
Article numberonco.13633
Pages (from-to)294-301
Number of pages8
JournalThe Oncologist
Issue number4
Early online date10-Dec-2020
Publication statusPublished - Apr-2021
Externally publishedYes

Cite this