Top

Published in:

01-01-2017 | Original Article

Efficacy and safety of everolimus and sunitinib in patients with gastroenteropancreatic neuroendocrine tumor

Authors: Changhoon Yoo, Hyungwoo Cho, Min Jeong Song, Seung-Mo Hong, Kyu-pyo Kim, Heung-Moon Chang, Heejung Chae, Tae Won Kim, Yong Sang Hong, Min-Hee Ryu, Yoon-Koo Kang, Song Cheol Kim, Baek-Yeol Ryoo

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2017

Abstract

Purpose

Efficacy of targeted agents, such as everolimus and sunitinib, has been demonstrated in prospective trials on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Considering the heterogeneous clinicopathological characteristics of neuroendocrine tumors (NETs), evaluation of treatment outcomes in a real-world setting is necessary.

Methods

Clinical records of 44 patients with GEP-NET who were treated with everolimus or sunitinib between March 2007 and October 2014 were retrospectively reviewed. Considering the distinct characteristics of pancreatic NETs (pNETs) and non-pancreatic gastrointestinal NETs (GI-NETs), efficacy analysis was performed separately.

Results

Pancreas was the most common primary site (n = 28, 64%), followed by rectum (n = 10, 23%) and stomach (n = 3, 7%). Sunitinib and everolimus were administered in 27 (61%) and 17 (39%) patients, respectively. In patients with pNET, median progression-free survival (PFS) with everolimus and sunitinib was 16.6 months (95% CI 8.0–25.1) and 8.0 months (95% CI 0.0–17.4), respectively (p = 0.51). Among non-pancreatic GI-NET patients, median PFS with everolimus and sunitinib was 14.7 months (95% CI 2.4–27.0) and 1.7 months (95% CI 0.5–3.0), respectively (p = 0.001). Compared to patients treated with everolimus, tumor grade 3 (30 vs. 0%) and history of prior cytotoxic chemotherapy (70 vs. 50%) were more common in patients treated with sunitinib.

Conclusions

Both everolimus and sunitinib were effective in GEP-NET patients. Outcomes of everolimus therapy in GEP-NETs were consistent with those reported elsewhere. Poor efficacy of sunitinib in non-pancreatic GI-NETs may be attributable to the baseline characteristics associated with poor clinical outcomes.

Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE et al (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063–3072CrossRefPubMed

Caplin ME, Pavel M, Ćwikła JB et al (2014) Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371:224–233CrossRefPubMed

Yao JC, Fazio N, Simron S, Buzzoni R et al (2016) 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 387:968–977CrossRefPubMed

Raymond E, Dahan L, Raoul JL et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513CrossRefPubMed

Pavel ME, Hainsworth JD, Baudin E, Peeters M et al (2011) 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 378:2005–2012CrossRefPubMed

Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT et al (2010) First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 117:268–275CrossRefPubMedPubMedCentral

Strosberg JR, Wolin EM, Chasen B, Kulke MH, Bushnell DL, Caplin ME et al (2016) NETTER-1 phase III: progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate. ASCO Meet Abstr 34:194

Kulke MH, Anthony LB, Bushnell DL, de Herder WW (2010) NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 39:735–752CrossRefPubMedPubMedCentral

Pavel M, O’’Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R et al (2016) ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 103:172–185CrossRefPubMed

10.

Bosman FT, Carneiro F, Hruban RH, Theise ND (2010) WHO classification of tumours of the digestive system. World Health Organization, Geneva

11.

Oh DY, Kim TW, Park YS, Shin SJ, Shin SH, Song EK et al (2012) Phase 2 study of everolimus monotherapy in patients with nonfunctioning neuroendocrine tumors or pheochromocytomas/paragangliomas. Cancer 118:6162–6170CrossRefPubMed

12.

Panzuto F, Rinzivillo M, Fazio N, de Braud F, Luppi G, Zatelli MC et al (2014) Real-world study of everolimus in advanced progressive neuroendocrine tumors. Oncologist 19:966–974CrossRefPubMedPubMedCentral

13.

Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523CrossRefPubMedPubMedCentral

14.

Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J et al (2008) Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 26:3403–3410CrossRefPubMed

15.

Grande E, Capdevila J, Castellano D, Teulé A, Durán I, Fuster J et al (2015) Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). Ann Oncol 26:1987–1993CrossRefPubMed

16.

Ahn HK, Choi JY, Kim KM, Kim H, Choi SH, Park SH et al (2013) Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours. Br J Cancer 109:1414–1419CrossRefPubMedPubMedCentral

17.

Phan AT, Halperin DM, Chan JA, Fogelman DR et al (2015) Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol 16:695–703CrossRefPubMedPubMedCentral

Title: Efficacy and safety of everolimus and sunitinib in patients with gastroenteropancreatic neuroendocrine tumor
Authors: Changhoon Yoo
Hyungwoo Cho
Min Jeong Song
Seung-Mo Hong
Kyu-pyo Kim
Heung-Moon Chang
Heejung Chae
Tae Won Kim
Yong Sang Hong
Min-Hee Ryu
Yoon-Koo Kang
Song Cheol Kim
Baek-Yeol Ryoo
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3215-3

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Rituximab to treat gemcitabine-induced hemolytic–uremic syndrome (HUS) in pancreatic adenocarcinoma: a case series and literature review

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer

A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors

Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway

Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma

First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children’s Oncology Group Phase 1/Pilot Consortium

Keynote webinar | Spotlight on antibody–drug conjugates in cancer