P1, N=32, Not yet recruiting, Immunwork, Inc.

P4, N=3, Completed, Sheba Medical Center | Unknown status --> Completed | N=10 --> 3

P3, N=202, Recruiting, ITM Solucin GmbH | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Jun 2027

P2, N=52, Not yet recruiting, Australasian Gastro-Intestinal Trials Group

Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.

P3, N=300, Active, not recruiting, Lund University Hospital | Not yet recruiting --> Active, not recruiting

Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide.

This rare case highlights the pathological complete response of initially unresectable multiple liver metastases achieved by PRRT and SSAs following PNET resection, suggesting their potential as a multimodality treatment option for unresectable PNET.

Fluorine-18 is widely used as a radionuclide for the production of radiopharmaceuticals for positron emission tomography (PET). Due to its short half-life (T1/2,109.8 min), its ease of production will facilitate the widespread dissemination of this radiopharmaceutical. A high-quality [AlF]NODA-MPAA-HTA was synthesized with satisfactory yield. This radiopharmaceutical demonstrated higher tumor uptake and better tumor-to-muscle contrast, resulting to excellent image quality. These findings suggest that the novel F-labeled somatostatin analogue, [AlF]NODA-MPAA-HTA, is a promising tool for PET imaging of NETs.

Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.

P3, N=309, Active, not recruiting, ITM Solucin GmbH | Trial completion date: Jun 2029 --> Dec 2029 | Trial primary completion date: Jun 2024 --> Dec 2024

P3, N=120, Recruiting, Grupo Espanol de Tumores Neuroendocrinos | Not yet recruiting --> Recruiting | Initiation date: Jul 2023 --> Oct 2023

Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.

LAR-SSA has an effect only on physiological organ uptake of 99m Tc-EDDA/HYNIC-TOC, reducing uptake. It has no significant effect on pathological uptake for most sites of primary and metastatic disease. This should be taken into account if making quantitative measurements, calculating T/B ratios or assigning Krenning Scores. There is the potential for improved dosimetric results in Peptide Receptor Radionuclide Therapy by maintaining patients on LAR-SSA.

While select laboratory and imaging modalities are available for diagnosis and monitoring of duodenal NET, this is the first reported therapeutic use of lanreotide in this NET setting. The observed serum chromogranin A attenuation, even before surgery, supports its effectiveness in management of primary nonmetastatic duodenal NET after resection.

P2, N=100, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

The lack of change in patient's perceptions of the disease, treatment, and supportive care information provided over the first 6 months of LAN treatment may suggest that physicians provided adequate information at the treatment initiation.

Long-acting SSAs are an effective and safe initial therapy of patients with well differentiated NET, allowing tumor growth as well as symptoms control for long-time in selected patients.

There was limited evidence supporting somatostatin analogs for lymphorrhea after axillary lymphadenectomy. Multicenter randomized controlled trials are needed to confirm the efficacy and safety of somatostatin analogs after axillary lymphadenectomy.

Nurses strongly preferred the user experience of the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. "Ease of use" and "comfortable to handle" were the most important syringe attributes, and performance rating was significantly higher with Somatuline Autogel versus Lanreotide Pharmathen syringe for all but one attribute.

Our data suggest that higher SSA concentrations do not have a negative effect on 68 Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUV max TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in 68 Ga-DOTATATE PET/CT imaging.

Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.

Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of Lu-iPSMA and Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

Initial data suggest promising efficacy. Part 2 (phase 3) is enrolling and will compare RYZ101 at 10.2MBq q8w for 4 cycles with standard of care in pts with advanced SSTR2+ GEP-NETs progressing following prior 177Lu-labeled SSAs.

P=N/A, N=95, Recruiting, Asan Medical Center | Trial primary completion date: Jan 2023 --> Jan 2024

P4, N=270, Recruiting, University Hospital, Antwerp | Not yet recruiting --> Recruiting

Standard starting dose of lanreotide 120 mg every 28 days was used in 66 patients...Overall, our findings were in keeping with current guidelines. It will be interesting to assess how clinical practice evolves in the future and to determine the role of dose escalation for disease control.

Herein, we report on the SST binding parameters measured toward intact mouse pheochromocytoma cells and corresponding cell homogenates and discuss the observed differences taking the physiology of SST and GPCRs in general into account. Furthermore, we point out method-specific advantages and limitations.

Most patients did not experience anxiety prior to their most recent injection and acknowledged that thanks to their treatment they had a good quality of life despite their disease. Most strongly agreed that the PSP met their medical needs, which highlights the valuable service that LAN PSPs provide for patients with NETs.

P3, N=120, Not yet recruiting, Grupo Espanol de Tumores Neuroendocrinos

No abstract available

IART with 177 Lu-DOTATATE significantly increases tumour dose while reducing overall systemic toxicity in comparison to SRT treatment. After considering the maximum tolerance limit of kidneys in peptide receptor radionuclide therapy, the number of treatment cycles and injected activity can be optimized further with IART for better response and survival.

Recent developments in radiochemistry have allowed a shift from Ga toward F labeling, leading to promising clinical translations of F-labeled SSAs, such as Gluc-Lys-[F]FP-TOCA, [F]F-FET-βAG-TOCA, [F]AlF-NOTA-octreotide, [F]SiTATE, and [F]AlF-NOTA-JR11. This review gives an update of currently available clinical data regarding F-labeled SSA tracers and provides justification for the clinical application of this class of tracers.

Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of GEP-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting (CTPM) in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included: 1) PRRT re-treatment; 2) PRRT and immunotherapy combinations; 3) PRRT and DNA damage repair inhibitor combinations; 4) Treatment for liver dominant disease; 5) Treatment for PRRT resistant disease; and 6) Dosimetry modified PRRT.

Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with Lu-DOTATATE.

In our study, we showed that SUVmax/Sx, RECIST, ∆TDTV + new lesion, and ∆TTLD + new lesion parameters can predict OS in the evaluation of response to treatment.

Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*

In this series of acromegalic patients with macroadenomas invading the cavernous sinus, neoadjuvant somatostatin analog therapy was associated with a trend toward increased rates of gross total resection and biochemical remission. Of note, those who were not in remission in the pretreatment group had a milder biochemical elevation and required lower-intensity medical therapy postoperatively. The systematic literature review and meta-analysis that we have performed confirm a statistically significant increase in remission rate in patients receiving neoadjuvant therapy.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation.

Nevertheless, preclinical and clinical studies on these radiopharmaceuticals are still few and heterogeneous, despite the growing momentum for their future use on a larger scale. In this context, this report provides a comprehensive and extensive overview of the development of Ac-labeled somatostatin analogs; particular emphasis is placed on the challenges associated with the production of Ac, its physical and radiochemical properties, as well as the place of Ac-DOTATOC and Ac-DOTATATE in the management of patients with advanced metastatic neuroendocrine tumors.