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: 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...