Update on Novel Therapies for Pancreatic Neuroendocrine Tumors: 2013
Neuroendocrine tumors of the pancreas (pNETs) are classified on the basis of their differentiation as well as the functional status. Current treatment options for non resectable disease include everolimus, sunitinib, somatostatin analogs and chemotherapy. A number of trials with novel compounds and drug combinations were reported at the recent ASCO Annual Meeting. Pasireotide is a novel somatostatin analog with broader affinity for the somatostatin receptors compared to the traditional octreotide and lantreotide and it appears to be safe in patients with pNETs according to a phase I study (Abstract #e15126). The combination of octreotide with everolimus showed promising response rate and progression free survival in a phase II study (Abstract #4136). In another phase II study, the AKT inhibitor MK-2206 was well tolerated with moderate efficacy (Abstract #e15133). Last but not least, we discuss the updated data from a phase II study that used the combination of temsirolimus with bevacizumab in patients with advanced pNETs (Abstract #4032).
Image: Albert Einstein Medical Center. Philadelphia, PA, USA.
Bergsland, E.K., The evolving landscape of neuroendocrine tumors. Semin Oncol, 2013. 40(1): p. 4-22.
Yao, J.C., M.P. Eisner, C. Leary, C. Dagohoy, A. Phan, A. Rashid, et al., Population-based study of islet cell carcinoma. Ann Surg Oncol, 2007. 14(12): p. 3492-500.
Gulati, A.P., B. Krantz, R.A. Moss, W.N. Moyal, D.A. Tsushima, K.B. Mowatt, et al., Treatment of multiple endocrine neoplasia 1/2 tumors: case report and review of the literature. Oncology, 2013. 84(3): p. 127-34.
Raymond, E., L. Dahan, J.L. Raoul, Y.J. Bang, I. Borbath, C. Lombard-Bohas, et al., Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med, 2011. 364(6): p. 501-13.
Yao, J.C., M.H. Shah, T. Ito, C.L. Bohas, E.M. Wolin, E. Van Cutsem, et al., Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med, 2011. 364(6): p. 514-23.
Rinke, A., H.H. Muller, C. Schade-Brittinger, K.J. Klose, P. Barth, M. Wied, et al., Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol, 2009. 27(28): p. 4656-63.
Wolin, E.M., PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors. Cancer Lett, 2013. 335(1): p. 1-8.
Chen, M., M. Van Ness, Y. Guo, and J. Gregg, Molecular pathology of pancreatic neuroendocrine tumors. J Gastrointest Oncol, 2012. 3(3): p. 182-8.
Oberg, K., Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors). Curr Opin Endocrinol Diabetes Obes, 2009. 16(1): p. 72-8.
Kulke, M.H., Systemic therapy for advanced pancreatic neuroendocrine tumors. Semin Oncol, 2013. 40(1): p. 75-83.
Reidy-Lagunes, D.L., Systemic therapy for advanced pancreatic neuroendocrine tumors: an update. J Natl Compr Canc Netw, 2012. 10(6): p. 777-83.
Reidy-Lagunes, D.L., M.C. Pietanza, M. Segal, M. Capanu, and L. Saltz, A phase II clinical and translational study of MK-2206 in patients with metastatic neuroendocrine tumors (NETs). J Clin Oncol 31, 2013 (suppl; abstr #e15133).
Phan, A., E.M. Wolin, J.A. Chan, J.M. Huang, M. Hudson, G. Hughes, et al., Phase I dose-escalation study of pasireotide LAR in patients with advanced neuroendocrine tumors. J Clin Oncol 31, 2013 (suppl; abstr #e15126).
Bajetta, E., L. Catena, N. Fazio, S. Pusceddu, P. Biondani, G. Blanco, et al., Everolimus in combination with octreotide LAR as the first-line treatment for advanced neuroendocrine tumors: A phase II trial of the I.T.M.O. (Italian Trials in Medical Oncology) group. J Clin Oncol 31, 2013 (suppl; abstr #4136).
Hobday, T.J., R. Qin, M. Moore, D.L. Reidy-Lagunes, J.R. Strosberg, H.L. Kindler, et al., Multicenter phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in pancreatic neuroendocrine tumor (pNET). J Clin Oncol 31, 2013 (suppl; abstr #4032).
Chan, J.A., D.P. Ryan, A.X. Zhu, T.A. Abrams, B.M. Wolpin, P. Malinowski, et al., Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors. Endocr Relat Cancer, 2012. 19(5): p. 615-23.
Pavel, M.E., J.D. Hainsworth, E. Baudin, M. Peeters, D. Horsch, R.E. Winkler, et al., Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet, 2011. 378(9808): p. 2005-12.
Hobday TJ, Qin R, Reidy DL, Moore MJ, Strosberg JR, Kaubisch A, et al. Multicenter phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in pancreatic neuroendocrine tumor (PNET). J Clin Oncol 2012; 30(Suppl.): Abstract #4047.
Copyright (c) 2014 Anastasios Dimou, Kostas N Syrigos, Muhammad Wasif Saif
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