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Background: Sunitinib, a multitarget tyrosine kinase inhibitor, showed encouraging antitumor activity and manageable toxicity in patients with advanced midgut neuroendocrine tumors (NETs) in earlier results from phase I and II trials. Patients and methods: In this phase II trial, patients with a nonresectable grade 1 or 2 midgut progressive NET and Eastern Cooperative Oncology Group performance status 0–1 were randomly assigned 1:1 to receive 37.5 mg sunitinib or a placebo, combined with 120 mg lanreotide autogel every 28 days. The planned sample size was 104 patients. The primary outcome was investigator-assessed progression-free survival (PFS). Results: The study was stopped early because of insufficient patient recruitment. Between January 2013 and December 2016, 44 patients were enrolled and received sunitinib (n = 22) or placebo (n = 22). The median age was 63.7 years (Q 1– Q 3 range, 56.6–68.1) and 26 patients (59.1%) were male. The main localization was ileum (N = 37, 84.1%) and the majority were grade 2 (n = 25, 56.8%). The median follow-up was 36.7 months (95% confidence interval (CI) 34.6–48.2). The median PFS was 9.84 months (95% CI 6.8–23.3) with sunitinib and 11.47 months (95% CI 5.4–15.3) with placebo (hazard ratio (HR) = 0.80, 95% CI 0.41–1.56, p = 0.51). There was no difference in overall survival between treatment arms (HR = 0.81, (95% CI 0.32–2.01), p = 0.64). The objective response rate was 9.1% with sunitinib and 0.0% with placebo, and 19 patients (86.4%) had stable disease. Thirty-nine patients (88.6%) completed the baseline QLQ-C30 questionnaire. Baseline health-related quality of life level was similar between treatment arms, except for physical and emotional functioning which were higher (p = 0.089) and lower (p = 0.023) in the sunitinib arm, respectively. Trends toward longer time until a definitive deterioration in favor of the sunitinib arm were observed for 10 out of 15 dimensions (HRs < 1), with a significant result for financial difficulties (HR = 0.31, (90% CI 0.10–0.94)). Twenty-seven patients (61.4%) had at least one adverse event grade ⩾3 (sunitinib: 72.7%, placebo: 50.0%), with only one patient grade 4 for hypertension and vomiting. Eleven deaths non-related to treatment occurred (sunitinib arm: n = 5, placebo arm: n = 6). Conclusion: Our study does not provide enough evidence to conclude the role of sunitinib in advanced midgut NETs, primarily due to a lower-than-expected number of enrolled patients. While we cannot entirely rule out the efficacy of sunitinib, lanreotide alone may play a significant role. Trial registration: EudraCT: 2012-001098-94. Plain language summary: SUNLAND: a randomized, double-blind phase II GERCOR trial of sunitinib versus placebo and lanreotide in patients with advanced progressive midgut neuroendocrine tumors Neuroendocrine tumours of the small intestine are a rare condition with a very different prognosis and treatment from the more "classic" tumours (known as intestinal adenocarcinomas). A wide variety of treatments can be proposed, depending on the extent of the disease, the specific characteristics of the tumour (degree of proliferation) and how far it has progressed. Treatments may include surgical removal of tumours, administration of hormones (somatostatin analogues), "conventional" chemotherapy agents (cytotoxics), targeted systemic treatments, embolisation/chemotherapy applied directly to liver metastases, radioactive agents (PPRT), etc. Sunitinib is a drug that prevents the synthesis of vessels by certain tumours, thereby preventing them from feeding and proliferating. We compared this drug with a placebo, in combination with a somatostatin analog named lanreotide (phase II study). The main objectives studied were the rate and duration of tumor control (named progression free survival or PFS, corresponding to the length of time during the treatment of a tumour that a patient lives with the disease but it does not get worse. In a clinical trials, this is one classical way to see how well a new treatment works) and the quality of life parameters. The full recruitment of 104 patients planned for this study performed in 11 French center could not be reached, no doubt because of the rarity of this disease and the existence, at the same time, of therapeutic trials with other treatments. Despite some favourable trends for sunitinib on quality of life, the study was not conclusive, partly due to the use of octreotide in all patients, which may have interfered with the experimental treatment. [ABSTRACT FROM AUTHOR]

Introduction: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. Methods: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. Results: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pretherapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P <0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cmin 25 cases. Surgical complications were more numerous (P= 0.001). In the subgroup analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P =0.977) and location (P =0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P =0.387). Conclusion: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours. [ABSTRACT FROM AUTHOR]

Introduction: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival., Methods: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group., Results: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P <0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous ( P =0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade ( P =0.977) and location ( P =0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion ( P =0.387)., Conclusion: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)