Endocrine Abstracts

One of the most important activating genetic aberrations in differentiated thyroid cancer (DTC) development pathways involves the RET/PTC–RAS–RAF–MAPK axis. Mutations in the RET gene are essential in medullary thyroid carcinoma (MTC). Sorafenib is the first compound to reach clinical practice that is capable of inhibiting all the RAF kinases. Moreover, it targets a panel of tyrosine kinase receptors, such as VEGF receptors which gives to sorafenib not only proap...

Background: SPINET was a phase 3 trial (NCT02683941) in patients with well-differentiated, advanced bronchopulmonary neuroendocrine tumors (NETs; typical and atypical carcinoids [TCs and ACs]). During the double-blind (DB) period, patients were randomized (2:1) to receive lanreotide autogel/depot (LAN; 120 mg) or placebo (PBO) every 28 days; in the optional open-label (OL) phase, all patients received LAN. Recruitment was stopped early due to slow accrual; all eligible patient...

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which frequently develop metastatic disease, represent an estimated 70% of NETs. There are limited treatment options with current standard therapies for well-differentiated aggressive grade 2 and grade 3 (Ki-67 index 15−55%) GEP-NETs; however, these may include somatostatin analogues; peptide receptor radionuclide therapy (PRRT); molecular targeted therapies (everolimus or sunitinib); chemotherapy; and ...

Background: Patients with advanced pheochromocytoma/paraganglioma (PPGL) or pancreatic neuroendocrine tumor (panNET) are in need of novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is one of the key oncogenic drivers in neuroendocrine tumors. Hypoxia signaling pathway alterations or other mechanisms that stabilize HIFs are common in some PPGLs and panNETs. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in advanced renal cell...

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent an estimated 70% of NETs. GEP-NETs frequently develop metastatic disease with limited treatment options. For well-differentiated high grade 2 and 3 GEP-NETs, current therapies include peptide receptor radionuclide therapy (PRRT), somatostatin analogues, chemotherapy, cytoreduction, and molecular targeted therapies (everolimus, sunitinib). PRRT uses radiolabeled somatostatin analogues to selectively t...

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: At a preplanned interim analysis (median follow-up 6.2 months) of the double-blind, phase 3 COSMIC-311 trial (NCT03690388), cabozantinib significantly improved progression-free survival (PFS) vs placebo (HR 0.22, 96% CI 0.13-0.36; P<0.0001) in 187 patients with previously treated radioiodine-refractory DTC (Brose, Lancet Oncol; 2021). Patients must have received lenvatinib or sorafenib and progressed during or after 1-2 prior VEGFR inhibitors. We prese...

Background: Increasing age is associated with poorer survival in DTC [Oyer SL, 2012]. In the phase 3 COSMIC-311 trial (NCT03690388), cabozantinib, an inhibitor of VEGFR2, MET, AXL and RET, significantly improved the progression-free survival (PFS) vs placebo in previously treated patients with RAI-R DTC (HR 0.22, 96% CI 0.13-0.36; P<0.0001; median follow-up 6.2 months). The impact of age on efficacy and safety was included in the prespecified subgroup analysis.</p...

Background: Delta-like ligand 3 (DLL3) is highly expressed on small-cell lung cancer (SCLC) tumors and neuroendocrine carcinomas (NECs). BI 764532 is a DLL3/CD3 IgG-like T-cell engager with potent preclinical activity. NCT04429087 is an ongoing phase I dose-escalation trial of BI 764532 in adults with locally advanced/metastatic DLL3-positive (confirmed centrally) SCLC, extrapulmonary NEC, or large cell neuroendocrine lung carcinoma. Here we focus on patients with extrapulmona...

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...