Phase 2 study of everolimus monotherapy in patients with nonfunctioning neuroendocrine tumors or pheochromocytomas/paragangliomas

Authors

  • Do-Youn Oh MD, PhD,

    1. Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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  • Tae-Won Kim MD, PhD,

    1. Department of Oncology, Asan Medical Center, Seoul, Korea
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  • Young Suk Park MD, PhD,

    1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea
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  • Sang Joon Shin MD,

    1. Division of Medical Oncology, Department of Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
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  • Seong Hoon Shin MD,

    1. Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
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  • Eun-Kee Song MD,

    1. Division of Hematology/Oncology, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
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  • Hyo Jin Lee MD,

    1. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
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  • Kewn-wook Lee MD, PhD,

    1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul, Korea
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  • Yung-Jue Bang MD, PhD

    Corresponding author
    1. Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
    • Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 110-744

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    • Fax: (011) 82-2-762-9662


  • Presented in part at the European Multidisciplinary Cancer Congress; September 23-27, 2011; Stockholm, Sweden.

Abstract

BACKGROUND:

The current study was conducted to evaluate the efficacy and safety of everolimus in the treatment of patients with nonfunctioning neuroendocrine tumors (NETs) or pheochromocytomas/paragangliomas.

METHODS:

Patients with histologically confirmed nonfunctioning NETs or pheochromocytomas/paragangliomas and with documented disease progression before study enrollment were eligible for the current study. Everolimus was administered daily at a dose of 10 mg for 4 weeks. Response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST; version 1.0) every 8 weeks. The primary endpoint was the 4-month progression-free survival rate (PFSR). The hypothesis of the current study was that the 4-month PFSR would increase from 50% to 65%. Safety was evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0).

RESULTS:

A total of 34 patients were enrolled. Of these, 27 patients had nonfunctioning NETs, 5 had pheochromocytomas, and 2 had paragangliomas. The 4-month PFSR was 78%. Partial response (PR) was observed in 3 patients. Twenty-eight patients had stable disease (SD) and 2 patients developed progressive disease (PD). The response rate (RR) and overall disease control rate (DCR) were 9.0% (95% confidence interval [95% CI], 0%-18.6%) and 93.9% (95% CI, 85.8%-100%), respectively. The PFS was 15.3 months (95% CI, 4.6 months-26.0 months). Of the patients with nonfunctioning NETs, 3 achieved a PR and 23 had SD (RR, 11.1%; DCR, 100%); the PFS was 17.1 months (95% CI, 11.1 months-23.0 months) and the 4-month PFSR was 90.0%. Twenty-one patients (80.8%) demonstrated tumor shrinkage. In 7 patients with pheochromocytomas/paragangliomas, 5 achieved SD, and 2 developed PD. The PFS was 3.8 months (95% CI, 0.5 months-7.0 months) and the 4-month PFSR was 42.9%. Four patients demonstrated tumor shrinkage. The major grade 3/4 adverse events were thrombocytopenia (14.7%), hyperglycemia (5.9%), stomatitis (5.9%), and anemia (5.9%).

CONCLUSIONS:

Everolimus was associated with high therapeutic efficacy and tolerability in patients with nonfunctioning NETs, and demonstrated modest efficacy in patients with pheochromocytomas/paragangliomas. Cancer 2012. © 2012 American Cancer Society.

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