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

Autor: Matthew H Kulke, Fang-Shu Ou, Donna Niedzwiecki, Lucas Huebner, Pamela Kunz, Hagen F Kennecke, Edward M Wolin, Jennifer A Chan, Eileen M O’Reilly, Jeffrey A Meyerhardt, Alan Venook
Rok vydání: 2022
Předmět:
Zdroj: Endocr Relat Cancer
ISSN: 1479-6821
1351-0088
DOI: 10.1530/erc-21-0239
Popis: Treatment with the mTOR inhibitor everolimus improves progression-free survival in pancreatic neuroendocrine tumors, 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 pancreatic neuroendocrine tumors. One hundred and fifty patients were randomized to receive everolimus 10 mg daily with or without bevacizumab 10 mg/kg IV every 2 weeks. Patients in both arms also received standard dose octreotide. The primary endpoint was progression-free survival, 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; 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 months 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 progression-free survival and higher response rates compared to everolimus in patients with advanced pancreatic neuroendocrine tumors. 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 pancreatic neuroendocrine tumors.
Databáze: OpenAIRE
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