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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kulke, MH; Ou, F-S; Niedzwiecki, D; Huebner, L; Kunz, P; Kennecke, HF; Wolin, EM; Chan, JA; O'Reilly, EM; Meyerhardt, JA; Venook, A

Published Date

  • May 9, 2022

Published In

Volume / Issue

  • 29 / 6

Start / End Page

  • 335 - 344

PubMed ID

  • 35324465

Pubmed Central ID

  • PMC9257687

Electronic International Standard Serial Number (EISSN)

  • 1479-6821

Digital Object Identifier (DOI)

  • 10.1530/ERC-21-0239

Language

  • eng

Conference Location

  • England