Endocrine Abstracts

Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly characterized by high-density expression of somatostatin receptors (SSTRs), which can be targeted by radiopharmaceutical therapy (RPT) via radiolabeled somatostatin analogues (SSAs). RYZ101 (225Ac-DOTATATE) is a first-in-class, highly potent alpha-emitting RPT being developed for the treatment of SSTR+ solid tumors. Alpha-particles (such as those emitted by 225<...

Background: Neuroendocrine tumors (NETs; ~2% of all malignancies) commonly arise from the GI tract, pancreas, and lung and often present with metastatic disease. The PI3K/Akt/mTOR pathway is implicated in the pathogenesis and progression of NETs. The oral mTOR inhibitor (mTORi), everolimus, is approved for treatment of patients with NETs of the GI tract, lung, or pancreas. However, due to the rarity and heterogeneity, nonspecific clinical symptoms, and unique indolent biology,...

Background: Metastatic GI Neuroendocrine Tumors (GI-NET) and pheochromocytoma/paraganglioma (PPGL) are are tumors which overexpresses somatostatin receptors (SSTR) and can be treated with targeted radioligand therapy (RLT) such as Lu-177-DOTATATE. However, despite demonstrated clinical efficacy at stabilizing tumor growth, durable response is very rare and almost all patients inevitably progresses at some time after treatment. Good systemic therapy options after beta-emiting R...

Background: nab-Sirolimus, approved in the US for patients with advanced malignant PEComa, is a novel albumin-bound mTOR inhibitor (mTORi) that inhibits the mTOR pathway via suppression of the mTORC1 complex. When TSC1 or TSC2 is inactivated via mutation or loss, the mTOR pathway may be aberrantly activated. TSC1 and TSC2 alterations occur in a range of common cancers. Clinically, in the AMPECT exploratory analysis of nab-sirolimus in advanced malignant PEComa (NCT02494570), 8...

Background: Everolimus is the only approved drug for patients with advanced bronchopulmonary neuroendocrine tumors (NET), and there is an urgent unmet need for alternative treatments. Retrospective data for peptide receptor radionuclide therapy (PRRT) have demonstrated promising activity in somatostatin receptor (SST)-positive lung NET. This study aims to investigate the clinical efficacy, safety, and patient-reported outcomes when 177Lu-edotreotide is used to treat...

Background: Targeted radionuclide therapies (TRTs) have changed the treatment paradigm of neuroendocrine tumors (NET) and are expected to be widely available for patients with various gastroenteropancreatic (GEP)-NET phenotypes. However, while they have great potential, TRT-based therapeutic strategies for high-grade GEP-NET demonstrate variable outcomes, and there is a current lack of tools to identify patients who are likely to respond to TRT. To address this need, the rando...

Background: Somatostatin receptors (SSTR) is overexpressed in a number of different tumors, including GI Neuroendocrine Tumors (GI-NET), Pheochromocytoma/Paraganglioma (PPGL), small cell lung cancer (SCLC), renal cell carcinoma (RCC), and certain head and neck cancers (H&N) such as olfactory neuroblastoma. It has been demonstrated that these SSTR-expressing tumors can be treated with beta-emitting radioligand therapy (RLT) that binds to SSTR such as Lu-177-DOTATATE. Howeve...

Acknowledgements: This study was funded by Camurus AB. Medical writing support was provided by Costello Medical and funded by Camurus AB.Background: Somatostatin receptor ligands (SRLs) are first-line standard of care therapies for gastroenteropancreatic neuroendocrine tumors (GEP-NET), showing efficacy in tumor/symptom control with an established safety profile. However, disease progression usually occurs despite standard-dose SRL treatment, requiring m...

Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The effi...

Background: Combination peptide receptor radionuclide therapy (PRRT) with the multikinase inhibitor cabozantinib may result in enhanced tumor response and improved intratumoral delivery of Lu-177 DOTATATE by normalization of tumor vasculature through VEGFR inhibition.Methods: In a phase Ib trial, patients with advanced somatostatin receptor (SSTR) positive, G1-3 neuroendocrine tumors (NETs) with a Krenning score of >2 are treated with 4 x 8 week cycl...

Background: 177Lu-DOTATATE is an FDA and Health Canada-approved treatment option for metastatic, progressive GEPNET patients. 177Lu-DOTATATE is now often considered the treatment of choice for small bowel/midgut patients who have progressed on somatostatin analogs (SSA). Despite 177Lu- DOTATATE’s impressive disease stabilization, many patients will eventually progress. Progression after prior use of PRRT does not necessarily render these tumors resistant to future PRRT tr...

Background: Finding relevant neuroendocrine tumor (NET) trials remains a challenge for patients and healthcare professionals (HCPs). Clinicaltrials.gov’s taxonomy associates many conditions with NETs, complicating the discovery process. As of 6/30/23 clinicaltrials.gov listed 700 recruiting, phase 1-3 interventional trials using the terms Neuroendocrine Tumors, Pheochromocytoma, and Paraganglioma. Many of these trials are not relevant for patients with NETs. Even with sev...