Novel Neuroendocrine Tumor (NET) Therapies

The placebo-controlled, prospective, phase III PROMID study evaluated the use of the somatostatin analoge, octreotide, in patients with advanced carcinoid tumors. Results showed that octreotide can help slow tumor growth, states Matthew H. Kulke, MD. The phase III RADIANT-4 clinical trial randomized individuals to receive everolimus or placebo plus best supportive care and demonstrated that mTOR inhibition via everolimus can also delay tumor progression.

Neuroendocrine tumors (NETs) are known to be vascular, which has led to the evaluation of angiogenesis inhibitors as viable treatment approaches, says Kulke. Sunitinib, a multi-targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor (VEGF) receptors, is known to be active in this setting. Pazopanib is another multi-targeted tyrosine kinase inhibitor highly targeted to VEGF that has been evaluated in a single-arm phase II study. Results indicated activity in pancreatic NETs and also suggested some activity in carcinoid tumors, he says.

Peptide receptor radionuclide therapy (PRRT) utilizes a radiopeptide that is attached to a somatostatin analog, which is then delivered to tumors throughout the body. The NETTER-1 study was the first randomized prospective study to formally evaluate PRRT in patients with advanced NETs, notes Kulke. Individuals enrolled in NETTER-1 had advanced carcinoid tumors and were randomized to receive either treatment with PRRT or high-dose octreotide that was not radiolabeled. The cohort that received PRRT demonstrated significantly improved progression-free survival.

Patients with advanced carcinoid tumors may be symptomatic from carcinoid syndrome, which is caused by high secretion of serotonin by the tumor and is manifested by flushing and diarrhea. Somatostatin analogs are effective as first-line treatment, but patients may become refractory over time, presenting with breakthrough diarrhea. This has generated interest in using direct inhibitors of serotonin to treat individuals with carcinoid syndrome. The phase III TELESTAR trial compared telotristat etiprate, a tryptophan hydroxylase inhibitor that blocks serotonin synthesis, with placebo. Results of TELESTAR showed that treatment with telotristat significantly decreases bowel movement frequency and diarrhea in patients with carcinoid syndrome.