Abstract Library

#4364 Single agent axitinib in the management of patients with progressive pheochromocytoma and paraganglioma

Introduction: Radiolabelled therapy with meta-iodobenzguanine (MIBG) and chemotherapy with a combination of cyclophosphamide, vincristine, and dacarbazine can help manage patients with metastatic pheochromocytoma and paraganglioma (mPPGL). The phase II FIRSTMAPPP study supports the use of the tyrosine kinase inhibitor sunitinib in these malignancies, with median progression-free survival values of 8.9 versus 3.6 months and overall response rates of 31% versus 8% for sunitinib versus placebo. The median duration of sunitinib therapy was 11 months. Concurrent with this study, we launched a single-arm trial to examine the activity of a similar tyrosine kinase inhibitor, axitinib.

Conference:

Presenting Author: Del Rivero J

Authors: Del Rivero J, Fojo T, Edgerly M, Pacak K, Figg W,

Keywords: PPGL, pheochromocytoma, paraganglioma, axitinib, TKI, tyrosinase kinase inhibitors,

#4282 A first-in-human phase I trial with antibody drug conjugate ADCT-701 in neuroendocrine tumours and carcinomas

Introduction: Neuroendocrine neoplasms (NENs) consist of neuroendocrine tumours and neuroendocrine carcinomas, which are rare malignancies found in various anatomical sites, including the gastrointestinal tract, pancreatic islets, lungs, and adrenal glands. Poorly differentiated NECs are classified as high-grade carcinomas that bear resemblance to small-cell lung cancer; however, these patients experience a high risk of relapse and demonstrate a limited response to additional systemic therapies. Adrenocortical carcinoma (ACC) is another rare cancer and currently, no targeted therapies have demonstrated significant effectiveness for this condition. Preclinical investigations have indicated that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in various neuroendocrine neoplasms, including ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma.

Conference:

Presenting Author: Del Rivero J

Authors: Del Rivero J, Glod J, Magee T, Cooper K, Rivero A,

Keywords: NEN, NEC, NET, ACC, ADC, ADCT-701,

#3512 Genetic, epigenetic and/or transcriptional profiling of 14q genes, MAX and MEG3 in pituitary neuroendocrine tumors

Introduction: Recent studies have identified a growing series of susceptibility genes for pituitary neuroendocrine tumors (PitNETs) and pheochromocytomas/paragangliomas (PPGL). Some of these genes (e.g., SDH genes) have be specifically associated with the development of these pathologies.

Conference:

Presenting Author: Ibáñez Costa A

Authors: Ibáñez-Costa A, Letón R, Rivero-Cortés E, Álvarez-Escolá C, Rodriguez Poyo-Guerrero P,

Keywords: pituitary tumor, epigenetics, MAX, genomics,

#3405 A phase 2 open-label study of belzutifan (a HIF-2α inhibitor) monotherapy in patients with advanced/metastatic pheochromocytoma/paraganglioma or pancreatic neuroendocrine tumors

Introduction: 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 like PPGL and somatostatinomas. 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 carcinoma and von Hippel-Lindau (VHL) disease–associated tumors, including panNET.

Conference:

Presenting Author:

Authors: Jimenez C, Hadoux J, Del Rivero J, Das S, Iliopoulos O,

Keywords: pheochromocytoma, paraganglioma, pancreatic neuroendocrine tumor, belzutifan, MK-6482, metastatic,

#3257 Molecular and functional study of somatostatin receptors in pheochromocytomas and paragangliomas

Introduction: Most pheochromocytomas (PCC) and paragangliomas (PGL) are benign neuroendocrine tumors that overproduce catecholamines causing hypertension, arrhythmia, and stroke; however, 10 30% may present distant metastasis. About 40% are caused by germline mutations, which may be classified in 3 different clusters. PCC/PGL diagnosis involves blood/urine tests and imaging techniques, while their treatment often requires distinct pharmacological and surgical approaches. Thus, identification of new biomarkers for early diagnosis, and progression/response would help to avoid unnecessary tests and enable personalized medicine approaches.

Conference: 18th Annual ENETS Concerence (2021)

Presenting Author: Ibáñez-Costa A

Authors: Ibáñez-Costa A, Blázquez-Encinas R, Alors-Pérez E, Fuentes-Fayos A, Rivero-Cortés E,

Keywords: pheochromocytoma, paraganglioma, somatostatin, somatostatin receptor, neuroendocrine tumor,