325
Views
9
CrossRef citations to date
0
Altmetric
Perspective

The emerging role of targeted therapies for advanced well-differentiated gastroenteropancreatic neuroendocrine tumors

, , &
Pages 101-108 | Received 20 Jul 2018, Accepted 17 Dec 2018, Published online: 16 Jan 2019

References

  • Weltgesundheitsorganisation, Lloyd RV, Osamura RY, et al. editors. WHO classification of tumours of endocrine organs. 4th ed. Lyon: International Agency for Research on Cancer; 2017.
  • Rinke A, Wittenberg M, 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 (PROMID): results of long-term survival. Neuroendocrinology. 2017;104:26–32.
  • Pavel ME, Hainsworth JD, Baudin E, 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;378:2005–2012.
  • Sadot E, Reidy-Lagunes DL, Tang LH, et al. Observation versus resection for small asymptomatic pancreatic neuroendocrine tumors: a matched case-control study. Ann Surg Oncol. 2016;23:1361–1370.
  • Yazici C, Boulay BR. Evolving role of the endoscopist in management of gastrointestinal neuroendocrine tumors. World J Gastroenterol. 2017;23:4847–4855.
  • Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer. 2015;121:1172–1186.
  • Saxena A, Chua TC, Perera M, et al. Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review. Surg Oncol. 2012;21:e131–141.
  • Zhang X-F, Beal EW, Chakedis J, et al. Early recurrence of neuroendocrine liver metastasis after curative hepatectomy: risk factors, prognosis, and treatment. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2017;21:1821–1830.
  • Elf A-K, Andersson M, Henrikson O, et al. Radioembolization versus bland embolization for hepatic metastases from small intestinal neuroendocrine tumors: short-term results of a randomized clinical trial. World J Surg. 2018;42:506–513.
  • Bloomston M, Al-Saif O, Klemanski D, et al. Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2007;11:264–271.
  • Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol. 2008;31:271–279.
  • Kennedy A, Bester L, Salem R, et al. Role of hepatic intra-arterial therapies in metastatic Neuroendocrine Tumours (NET): guidelines from the NET-liver-metastases consensus conference. London, HPB; 2015;17:29–37.
  • Mohan H, Nicholson P, Winter DC, et al. Radiofrequency ablation for neuroendocrine liver metastases: a systematic review. J Vasc Interv Radiol. 2015;26:935–942.e1.
  • Arrese D, McNally ME, Chokshi R, et al. Extrahepatic disease should not preclude transarterial chemoembolization for metastatic neuroendocrine carcinoma. Ann Surg Oncol. 2013;20:1114–1120.
  • Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer. 2005;104:1590–1602.
  • Do Minh D, Chapiro J, Gorodetski B, et al. Intra-arterial therapy of neuroendocrine tumour liver metastases: comparing conventional TACE, drug-eluting beads TACE and yttrium-90 radioembolisation as treatment options using a propensity score analysis model. Eur Radiol. 2017;27:4995–5005.
  • Arnold R, Trautmann ME, Creutzfeldt W, et al. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut. 1996;38:430–438.
  • Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. J Natl Compr Cancer Netw. 2015;13: 109–117. quiz 117.
  • Merola E, Panzuto F, Delle Fave G. Antiproliferative effect of somatostatin analogs in advanced gastro-entero-pancreatic neuroendocrine tumors: a systematic review and meta-analysis. Oncotarget. 2017;8:46624–46634.
  • Rinke A, Müller -H-H, 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;27:4656–4663.
  • Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224–233.
  • Alonso-Gordoa T, Capdevila J, Grande E. GEP-NETs update: biotherapy for neuroendocrine tumours. Eur J Endocrinol. 2015;172:R31–46.
  • Lamarca A, Barriuso J, McNamara MG, et al. Telotristat ethyl: a new option for the management of carcinoid syndrome. Expert Opin Pharmacother. 2016;17:2487–2498.
  • Kvols LK, Oberg KE, O’Dorisio TM, et al. Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocr Relat Cancer. 2012;19:657–666.
  • Wolin EM, Jarzab B, Eriksson B, et al. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Des Devel Ther. 2015;9:5075–5086.
  • Vitale G, Dicitore A, Sciammarella C, et al. Pasireotide in the treatment of neuroendocrine tumors: a review of the literature. Endocr Relat Cancer. 2018;25:R351–R364.
  • Broder LE, Carter SK. Pancreatic islet cell carcinoma. II. Results of therapy with streptozotocin in 52 patients. Ann Int Med. 1973;79:108–118.
  • 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, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326:519–523.
  • Cives M, Ghayouri M, Morse B, et al. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2016;23:759–767.
  • Kunz P. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211). J Clin Oncol. 2018;36(15_suppl):4004-4004. DOI:10.1200/JCO.2018.36.15_suppl.4004
  • Raj N, Klimstra DS, Horvat N, et al. O6-Methylguanine DNA methyltransferase status does not predict response or resistance to alkylating agents in well-differentiated pancreatic neuroendocrine tumors. Pancreas. 2017;46:758–763.
  • Milione M, Maisonneuve P, Spada F, et al. The clinicopathologic heterogeneity of grade 3 gastroenteropancreatic neuroendocrine neoplasms: morphological differentiation and proliferation identify different prognostic categories. Neuroendocrinology. 2017;104:85–93.
  • Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol Off J Eur Soc Med Oncol. 2013;24:152–160.
  • Coriat R, Walter T, Terris B, et al. Gastroenteropancreatic well-differentiated grade 3 neuroendocrine tumors: review and position statement. Oncologist. 2016;21:1191–1199.
  • Fazio N, Milione M. Heterogeneity of grade 3 gastroenteropancreatic neuroendocrine carcinomas: new insights and treatment implications. Cancer Treat Rev. 2016;50:61–67.
  • Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–523.
  • Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387:968–977.
  • Pavel ME, Singh S, Strosberg JR, et al. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1411–1422.
  • Bainbridge HE, Larbi E, Middleton G. Symptomatic control of neuroendocrine tumours with everolimus. Horm Cancer. 2015;6:254–259.
  • Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360:195–197.
  • Raymond E, Dahan L, Raoul J-L, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–513.
  • Vinik A, Bottomley A, Korytowsky B, et al. Patient-reported outcomes and quality of life with sunitinib versus placebo for pancreatic neuroendocrine tumors: results from an international phase III trial. Target Oncol. 2016;11:815–824.
  • Angelousi A, Kamp K, Kaltsatou M, et al. Sequential everolimus and sunitinib treatment in pancreatic metastatic well-differentiated neuroendocrine tumours resistant to prior treatments. Neuroendocrinology. 2017;105:394–402.
  • Kulke MH, Lenz H-J, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26:3403–3410.
  • Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA. 2011;305:487–494.
  • Yao JC, Guthrie KA, Moran C, et al. Phase III prospective randomized comparison trial of depot octreotide plus interferon Alfa-2b versus depot octreotide plus bevacizumab in patients with advanced carcinoid tumors: SWOG S0518. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35:1695–1703.
  • Mitry E, Walter T, Baudin E, et al. Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial)–a phase II non-randomised trial. Eur J Cancer Oxf Engl. 2014;50:3107–3115.
  • Ducreux M, Dahan L, Smith D, et al. Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)–a phase II non-randomised trial. Eur J Cancer Oxf Engl. 2014;50:3098–3106.
  • Kunz PL, Balise RR, Fehrenbacher L, et al. Oxaliplatin-fluoropyrimidine chemotherapy plus bevacizumab in advanced neuroendocrine tumors: an analysis of 2 phase II trials. Pancreas. 2016;45:1394–1400.
  • Abdel-Rahman O, Fouad M. Bevacizumab-based combination therapy for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a systematic review of the literature. J Cancer Res Clin Oncol. 2015;141:295–305.
  • Hobday TJ, Qin R, Reidy-Lagunes D, et al. Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33:1551–1556.
  • Ahn HK, Choi JY, Kim K-M, et al. Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours. Br J Cancer. 2013;109:1414–1419.
  • Phan AT, Halperin DM, Chan JA, et al. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol. 2015;16:695–703.
  • Grande E, Capdevila J, Castellano D, et al. Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish task force Group for Neuroendocrine Tumors (GETNE). Ann Oncol Off J Eur Soc Med Oncol. 2015;26:1987–1993.
  • Chan JA, Faris JE, Murphy JE, et al. Phase II trial of cabozantinib in patients with carcinoid and pancreatic neuroendocrine tumors (pNET). J Clin Oncol. 2017;35:228.
  • Grillo F, Florio T, Ferraù F, et al. Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms. Endocr Relat Cancer. 2018;25:R453–R466.
  • Kim S-J, Pak K, Koo PJ, et al. The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging. 2015;42:1964–1970.
  • Brabander T, van der Zwan WA, Teunissen JJM, et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res Off J Am Assoc Cancer Res. 2017;23:4617–4624.
  • Kunikowska J, Pawlak D, Bąk MI, et al. Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study. Ann Nucl Med. 2017;31:347–356.
  • Parghane RV, Talole S, Prabhash K, et al. Clinical response profile of metastatic/advanced pulmonary neuroendocrine tumors to peptide receptor radionuclide therapy with 177Lu-DOTATATE. Clin Nucl Med. 2017;42:428–435.
  • Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–135.
  • Strosberg J, Wolin E, Chasen B, et al. Health-related quality of life in patients with progressive midgut neuroendocrine tumors treated with 177Lu-dotatate in the phase III NETTER-1 trial. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(25):2578–2584.
  • Ballal S, Yadav MP, Damle NA, et al. Concomitant 177Lu-DOTATATE and capecitabine therapy in patients with advanced neuroendocrine tumors: a long-term-outcome, toxicity, survival, and quality-of-life study. Clin Nucl Med. 2017;42:e457–e466.
  • Claringbold PG, Price RA, Turner JH. Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother Radiopharm. 2012;27:561–569.
  • Yordanova A, Wicharz MM, Mayer K, et al. The role of adding somatostatin analogues to peptide receptor radionuclide therapy as a combination and maintenance therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2018;24:4672–4679.
  • Nonnekens J, van Kranenburg M, Beerens CEMT, et al. Potentiation of peptide receptor radionuclide therapy by the PARP inhibitor olaparib. Theranostics. 2016;6:1821–1832.
  • Garske-Román U, Sandström M, Fröss Baron K, et al. Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018;45:970–988.
  • Smit Duijzentkunst DA, Kwekkeboom DJ, Bodei L. Somatostatin receptor 2-targeting compounds. J Nucl Med Off Publ Soc Nucl Med. 2017;58:54S–60S.
  • Kratochwil C, Giesel FL, Bruchertseifer F, et al. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience. Eur J Nucl Med Mol Imaging. 2014;41:2106–2119.
  • Arora G, Dubey P, Shukla J, et al. Evaluation of cytotoxic and tumor targeting capability of (177)Lu-DOTATATE-nanoparticles: a trailblazing strategy in peptide receptor radionuclide therapy. Ann Nucl Med. 2016;30:334–345.
  • Chauhan A, Horn M, Magee G, et al. Immune checkpoint inhibitors in neuroendocrine tumors: A single institution experience with review of literature. Oncotarget. 2018;9:8801–8809.
  • Auernhammer CJ, Spitzweg C, Angele MK, et al. Advanced neuroendocrine tumours of the small intestine and pancreas: clinical developments, controversies, and future strategies. Lancet Diabetes Endocrinol. 2018;6:404–415.
  • Yu D, Leja-Jarblad J, Loskog A, et al. Preclinical evaluation of AdVince, an oncolytic adenovirus adapted for treatment of liver metastases from neuroendocrine cancer. Neuroendocrinology. 2017;105:54–66.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.