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

Authors

Sonia M. Abuzakhm, OhioHealth, Columbus, Ohio, USA.
Vineeth Sukrithan, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Briant Fruth, Mayo Clinic, Rochester, Minnesota, USA.
Rui Qin, Janssen Pharmaceuticals, Raritan, New Jersey, USA.
Jonathan Strosberg, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Timothy J. Hobday, Mayo Clinic, Rochester, Minnesota, USA.
Thomas Semrad, Tahoe Forest Cancer Center, Truckee, California, USA.
Diane Reidy-Lagunes, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Hedy Lee Kindler, University of Chicago Medical Center, Chicago, Illinois, USA.
George P. Kim, George Washington University Cancer Center, Washington, DC, USA.
Jennifer J. Knox, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Andreas Kaubisch, Montefiore Medical Center, Bronx, New York, USA.
Miguel Villalona-Calero, City of Hope, Duarte, California, USA.
Helen Chen, CTEP National Cancer Institute, Bethesda, Maryland, USA.
Charles Erlichman, Mayo Clinic, Rochester, Minnesota, USA.
Manisha H. Shah, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.

Document Type

Journal Article

Publication Date

11-1-2023

Journal

Endocrine-related cancer

Volume

30

Issue

11

DOI

10.1530/ERC-22-0301

Keywords

bevacizumab; carcinoid; mTOR inhibitor; neuroendocrine; temsirolimus

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.

APA Citation

Abuzakhm, Sonia M.; Sukrithan, Vineeth; Fruth, Briant; Qin, Rui; Strosberg, Jonathan; Hobday, Timothy J.; Semrad, Thomas; Reidy-Lagunes, Diane; Kindler, Hedy Lee; Kim, George P.; Knox, Jennifer J.; Kaubisch, Andreas; Villalona-Calero, Miguel; Chen, Helen; Erlichman, Charles; and Shah, Manisha H., "A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors" (2023). GW Authored Works. Paper 3321.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3321

Department

Medicine