Novel Agents in the Treatment of Unresectable Neuroendocrine Tumors

  • Paul E Oberstein Columbia University College of Physicians and Surgeons at New York Presbyterian Hospital. New York, NY, USA
  • Muhammad Wasif Saif Columbia University College of Physicians and Surgeons at New York Presbyterian Hospital. New York, NY, USA
Keywords: Drug Therapy, everolimus, Neuroendocrine Tumors, Pancreatic Neoplasms

Abstract

Pancreatic neuroendocrine tumors represent a small percentage of all pancreatic tumors (1.3%) but their incidence is rising. Prior to 2011, the only approved agent for unresectable disease was streptozicin (often used in combination with doxorubicin) but the efficacy of this drug is in question and there had not been any new drugs approved for this disease in more than 20 years. Recently there has been new excitement for the treatment of advanced neuroendocrine tumors including those of the pancreas (pNET) with FDA approval of 2 new agents in 2011. One of these agents was everolimus, an mTOR inhibitor, which was approved on the basis of a landmark phase III study (RADIANT-3). At the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, several abstracts were presented reviewing novel agents in the treatment of advanced NET. Three abstracts looked at characteristics of patients treated on the RADIANT-3 study and looked at the role of prior chemotherapy use (Abstract #4103), somatostatin analog use (Abstract #4010), and updated safety data (Abstract #4009) from this trial. Additionally, an abstract was presented (Abstract 4008) looking at updated data from the other targeted agent approved for advanced pNET, sunitinib, a multi-tyrosine kinase inhibitor, which demonstrated improvement in progression-free survival compared to placebo. Novel agents were also presented, including a phase II trial looking at the combination of sorafenib and bevacizumab (Abstract #4113), and a phase I trial looking at a novel somatostatin analog, pasireotide, in combination with everolimus (Abstract #4120) The authors review and summarize these abstracts in this article.

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References

Yao JC, Eisner MP, Leary C, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol 2007; 14:3492-3500.

Zhou J, Enewold L, Stojadinovic A, et al. Incidence rates of exocrine and endocrine pancreatic cancers in the United States. Cancer Causes Control 2010; 21:853-861.

Yao JC, Hassan M, Phan A, et al. One hundred years after ''carcinoid'': epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26:3063-72.

Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med 1980; 303:1189-1194.

Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil, or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992; 326:519-523.

McCollum AD, Kulke MH, Ryan DP, Clark JW, Shulman LN, Mayer RJ, et al. Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors. Am J Clin Oncol 2004; 27:485-8.

Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 2008; 135:1469-1492.

Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer 2008; 113:2655-2664.

Shah MH, Ito T, Lombard-Bohas C, Wolin EM, Van Cutsem E, Sachs C, et al. Everolimus in patients with advanced pancreatic neuroendocrine tumors: Updated results of a randomized, double-blind, placebo-controlled multicenter phase III trial (RADIANT-3). J Clin Oncol 2011, 29(Suppl. 4):158.

Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011; 364:514-23.

Raymond E, Dahan L, Raoul J-L, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011; 364:501-13.

Shah MH, Lombard-Bohas C, Ito T, et al. Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Impact of somatostatin analog use on progression-free survival in the RADIANT-3 trial. J Clin Oncol 2011; 29(Suppl.):4010.

Pommier RF, Wolin EM, Panneerselvam A, et al. Impact of prior chemotherapy on progression-free survival in patients (pts) with advanced pancreatic neuroendocrine tumors (pNET): Results from the RADIANT-3 trial. J Clin Oncol 2011; 29(Suppl.):4103.

Strosberg JR, Lincy J, Winkler RE, et al. Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter, phase III trial (RADIANT-3). J Clin Oncol 2011; 29(Suppl.):4009.

Raymond E, Niccoli P, Raoul J, et al. Updated overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) of sunitinib (SU) versus placebo (PBO) for patients (Pts) with advanced unresectable pancreatic neuroendocrine tumors (NET). J Clin Oncol 2011; 29(Suppl.):4008.

Chan JA, Ryan DP, Fuchs CS, et al. Updated results of a phase I study of pasireotide (SOM230) in combination with everolimus (RAD001) in patients (pts) with advanced neuroendocrine tumors (NET). J Clin Oncol 2011; 29(Suppl.):4120.

Castellano DE, Capdevila J, Salazar R, et al. Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumor: A phase II study of the Spanish Neuroendocrine Tumor Group (GETNE0801). J Clin Oncol 2011; 29(Suppl.):4113.

Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005; 8:299-309.

Rinke A, Muller HH, Schade-Brittinger C, 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; 27:4656-63.

Pavel M, Hainsworth JD, Baudin E, Peeters M, Hoersch D, Anthony L, et al. A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR vs placebo + octreotide LAR in patients with advanced neuroendocrine tumors (NET) (RADIANT-2). Ann Oncol 2010; 21(Suppl 8):viii4.

Yao JC, Ricci S, Winkler RE et al. Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients with advanced neuroendocrine tumors (NET): Updated safety and efficacy results from RADIANT-2. J Clin Oncol 2011; 29(Suppl.):4011.

Anthony LB, Peeters M, Hainsworth JD et al. Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients with advanced neuroendocrine tumors (NET): Effect of prior somatostatin analog therapy on progression-free survival in the RADIANT-2 trial. J Clin Oncol 2011; 29(Suppl.):4078.

Wolin EM, Fazio N, Saletan S et al. Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients with advanced neuroendocrine tumors: Analysis by primary tumor site from RADIANT-2. J Clin Oncol 2011; 29(Suppl.):4075.

Mosaic in the 116th Street station of the New York subway system
Published
2011-07-08
How to Cite
ObersteinP., & SaifM. (2011). Novel Agents in the Treatment of Unresectable Neuroendocrine Tumors. JOP. Journal of the Pancreas, 12(4), 358-361. https://doi.org/10.6092/1590-8577/3081
Section
Highlights from the “2011 ASCO Annual Meeting”. Chicago, IL, USA. June 3-7, 2011