Lanreotide Therapy vs Active Surveillance in MEN1-Related Pancreatic Neuroendocrine Tumors < 2 Centimeters

Abstract

Purpose Pancreatic neuroendocrine tumors (pNETs) are frequent in multiple endocrine neoplasia type 1 (MEN1) syndrome. They are usually not surgically treated unless larger than 1 to 2 cm or a growth rate > 0.5 cm per year. Somatostatin analogues represent one of the main therapeutic options in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs < 2 cm. Methods MEN1 patients with 1 or more pNETs < 2 cm of maximal diameter were considered. Study design was prospective observational, comparing patients treated with lanreotide autogel 120 mg every 28 days (LAN group) and patients in active surveillance, not receiving any therapy (AS group). Results Forty-two patients were enrolled: 23 in LAN and 19 in AS group. Median follow-up was 73 months. Initial imaging identified a total of 91 pNETs. The median progression-free survival was significantly longer in the LAN than in the AS group (median not reached vs 40 months, P < 0.001). In the LAN group, 4 patients had an objective tumor response, 15 patients had stable disease, while 4 had tumor progression. In the AS group, 13 patients had pNET progression, while 6 were stable. Conclusions This is the first prospective study evaluating the efficacy of somatostatin analogues in MEN1-related pNETs. These findings highlight that lanreotide autogel is effective as antiproliferative therapy in MEN1-related pNETs < 2cm, suggesting the utility of somatostatin analogues to arrest the development of tumor lesions as well as to delay or avoid pancreatic surgery.

Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs)

“…Pasireotide decreased proliferation and increased apoptosis of pNENs, suppressed tumour growth and tumor number, increased mice survival and resulted in prevention of tumor development. These results suggest the potential utility of SSAs such as pasireotide as chemo-preventive or prophylactic treatment of pancreatic and pituitary NENs in patients with MEN1, as supported by some recent clinical data (Cioppi et al 2017, Faggiano et al 2020. Further prospective studies of the effects of SOM230 in MEN1-NENs patients are warranted.…”

“…Prior to 1980, ~80% of MEN1-related deaths were caused by gastrinoma-derived gastric acid hypersecretion inducing multiple gastro-intestinal ulcers, bleeding and perforation; improvements in pharmacological control of the hypergastrinemia and related gastric acid hypersecretion have strongly reduced mortality related to these complications. Noteworthy, most of MEN1-related pancreatic or thymic NENs patients (~70-90%) will require therapeutic intervention during their life with the disease, including surgery and/or systemic therapy (somatostatin analogues, peptide-receptor radioligand therapy, everolimus, loco-regional therapies or chemotherapy) due to tumor progression/recurrence/multi-focality (De Laat et al 2014, Faggiano et al 2020, Oleinikov et al 2020. Despite the advances in their treatment, the life expectancy of MEN1-patients remains shorter than normal population (mean age at death ~55 years) (Norton et al 2015), with death prevalently occurring as result of the malignant progression of pancreatic and thymic NENs, which are responsible for ~50% and ~24% of fatalities, respectively (Marini et al 2017).…”

Somatostatin Analogs in Clinical Practice: A Review

“…In addition, in the lanreotide group, 17.4% of patients had an objective tumor response, 35.5% of patients had a variable degree of tumor shrinkage, 65.2% patients had a stable disease, and 100% of patients normalized baseline CgA levels. Only three patients in the lanreotide ATG group experienced mild adverse effects (G1 diarrhea and asymptomatic cholelithiasis) [129].…”

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

“…Regarding pNET, enucleation, Whipple resection, or distal pancreatectomy/splenectomy are recommended in case of symptoms, intermediate-to-high grades (G2-G3), or measure greater than 2 cm. Conversely, if smaller than 2 cm, low-grade, and nonfunctioning, pNET can be monitored according to a "watch-and-wait" strategy [12,68]. Regarding small intestinal NET, partial small bowel resections are usually performed for jejunal or proximal ileal tumors, whereas right hemicolectomy is indicated for tumors arising in or near the ileocecal valve [69].…”