Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance)

in Endocrine-Related Cancer
Authors:
Matthew H KulkeSection of Hematology and Medical Oncology, Boston University and Boston Medical Center, Boston, Massachusetts, USA

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https://orcid.org/0000-0001-8556-3977
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Fang-Shu OuAlliance Statistics and Data Management Center and Mayo Clinic Cancer Center, Rochester, Minnesota, USA

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Donna NiedzwieckiDepartment of Biostatistics, Duke Cancer Center, Durham, North Carolina, USA

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Lucas HuebnerAlliance Statistics and Data Management Center and Mayo Clinic Cancer Center, Rochester, Minnesota, USA

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Pamela KunzYale Cancer Center, New Haven, Connecticut, USA

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https://orcid.org/0000-0003-1613-3919
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Hagen F KenneckeVirginia Mason Cancer Institute, Seattle, Washington, USA

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Edward M WolinTisch Cancer Institute, New York, New York, USA

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Jennifer A ChanDana-Farber Cancer Institute, Boston, Massachusetts, USA

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Eileen M O’ReillyMemorial Sloan Kettering Cancer Center, New York, New York, USA

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Jeffrey A MeyerhardtDana-Farber Cancer Institute, Boston, Massachusetts, USA

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Alan VenookUCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA

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Correspondence should be addressed to M H Kulke: Matthew.Kulke@bmc.org
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Treatment with the MTOR inhibitor everolimus improves progression-free survival (PFS) in pancreatic neuroendocrine tumors (pNETs), but it is not known if the addition of a VEGF pathway inhibitor to an MTOR inhibitor enhances antitumor activity. We performed a randomized phase II study evaluating everolimus with or without bevacizumab in patients with advanced pNETs. One hundred and fifty patients were randomized to receive everolimus 10 mg daily with or without bevacizumab 10 mg/kg i.v. every 2 weeks. Patients also received standard dose of octreotide in both arms. The primary endpoint was PFS, based on local investigator review. Treatment with the combination of everolimus and bevacizumab resulted in improved progression-free survival compared to everolimus (16.7 months compared to 14.0 months; one-sided stratified log-rank P  = 0.1028; hazard ratio (HR) 0.80 (95% CI 0.56–1.13)), meeting the predefined primary endpoint. Confirmed tumor responses were observed in 31% (95% CI 20%, 41%) of patients receiving combination therapy, as compared to only 12% (95% CI 5%, 19%) of patients receiving treatment with everolimus (P = 0.0053). Median overall survival duration was similar in the everolimus and combination arm (42.5 and 42.1 months, respectively). Treatment-related toxicities were more common in the combination arm. In summary, treatment with everolimus and bevacizumab led to superior PFS and higher response rates compared to everolimus in patients with advanced pNETs. Although the higher rate of treatment-related adverse events may limit the use of this combination, our results support the continued evaluation of VEGF pathway inhibitors in pNETs.

 

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