Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Sep 13;30(11):e220301.
doi: 10.1530/ERC-22-0301. Print 2023 Nov 1.

A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors

Sonia M Abuzakhm  1 , Vineeth Sukrithan  2 , Briant Fruth  3 , Rui Qin  4 , Jonathan Strosberg  5 , Timothy J Hobday  3 , Thomas Semrad  6 , Diane Reidy-Lagunes  7 , Hedy Lee Kindler  8 , George P Kim  9 , Jennifer J Knox  10 , Andreas Kaubisch  11 , Miguel Villalona-Calero  12 , Helen Chen  13 , Charles Erlichman  3 , Manisha H Shah  2
Affiliations
Clinical Trial

A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors

Sonia M Abuzakhm et al. Endocr Relat Cancer. .

Abstract

We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity. Temsirolimus 25 mg was administered i.v. on days 1, 8, 15, and 22 and bevacizumab 10 mg/kg i.v. on days 1 and 15 of a 4-week cycle. Discontinuation of temsirolimus or bevacizumab did not require discontinuation of the other agent. The primary endpoints were objective response rate and 6-month progression-free survival rate. Fifty-nine patients were enrolled in this study, and 54 were evaluated for efficacy and adverse events. While median progression-free survival was 7.1 months, the median duration of treatment with temsirolimus was 3.9 months and that with bevacizumab was 3.5 months. The objective response rate of combination therapy was 2%, and 6-month progression-free survival was 48%. The most frequently reported grade 3-4 adverse events included fatigue (13%), hypertension (13%), and bleeding (13%). Close to 54% of the patients discontinued treatment due to adverse events, refusal of further treatment, or treatment delays. Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.

Keywords: bevacizumab; carcinoid; mTOR inhibitor; neuroendocrine; temsirolimus.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interest

Jonathan Strosberg: Honoraria from Speaker’s Bureau from Genentech; Jennifer J. Knox: Commercial research support from Pfizer for an investigator-initiated study; Manisha Shah: Commercial research grant from Novartis and consult/advisory board for Novartis; Vineeth Sukrithan: Research funding (to institution) from Eli Lilly & Company, consulting fees from GE Health and Lantheus. The remaining authors have no conflicts to disclose.

Figures

Figure 1.
Figure 1.
CONSORT Diagram
Figure 2.
Figure 2.
Waterfall Plot of Best Response
Figure 3.
Figure 3.
Kaplan-Meier Curve Estimating PFS
Figure 4:
Figure 4:
Kaplan-Meier Curve Estimating OS
See this image and copyright information in PMC

References

    1. BANCK MS, KANWAR R, KULKARNI AA, BOORA GK, METGE F, KIPP BR, ZHANG L, THORLAND EC, MINN KT, TENTU R, ECKLOFF BW, WIEBEN ED, WU Y, CUNNINGHAM JM, NAGORNEY DM, GILBERT JA, AMES MM & BEUTLER AS 2013. The genomic landscape of small intestine neuroendocrine tumors. J Clin Invest, 123, 2502–8. - PMC - PubMed
    1. CAPELLA C SE, SOBIN LH et al. ENDOCRINE TUMOURS OF THE SMALL INTESTINE. IN: HAMILTON SR, AALTONEN LA, EDS. PATHOLOGY AND GENETICS OF TUMOURS OF THE DIGESTIVE SYSTEM. LYON, FRANCE: IARC PRESS; 2000:77–82.
    1. CAPLIN ME, PAVEL M, ĆWIKŁA JB, PHAN AT, RADERER M, SEDLÁČKOVÁ E, CADIOT G, WOLIN EM, CAPDEVILA J, WALL L, RINDI G, LANGLEY A, MARTINEZ S, BLUMBERG J & RUSZNIEWSKI P 2014. Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors. New England Journal of Medicine, 371, 224–233. - PubMed
    1. DASARI A, SHEN C, HALPERIN D, ZHAO B, ZHOU S, XU Y, SHIH T & YAO JC 2017. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol, 3, 1335–1342. - PMC - PubMed
    1. DURAN I, KORTMANSKY J, SINGH D, HIRTE H, KOCHA W, GOSS G, LE L, OZA A, NICKLEE T, HO J, BIRLE D, POND GR, ARBOINE D, DANCEY J, AVIEL-RONEN S, TSAO MS, HEDLEY D & SIU LL 2006. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer, 95, 1148–54. - PMC - PubMed

Publication types

MeSH terms

Associated data