Journal article
Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016)
Sarcoma, Vol.2019, pp.1-8
07/24/2019
DOI: 10.1155/2019/7656747
PMCID: PMC6681622
PMID: 31427883
Abstract
Purpose
. There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months).
Patients and Methods
. Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active.
Results
. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1–16). Adverse events were similar to those known for this combination.
Conclusion
. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study’s target response rate and is not considered active in refractory MPNST.
Details
- Title: Subtitle
- Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016)
- Creators
- Brigitte C. Widemann - National Cancer Institute, Center for Cancer Research, Pediatric Oncology Branch, 10 Center Drive, Building 10, Room 1-3752, Bethesda, MD 20892, USA.Yao Lu - Cornell UniversityDenise Reinke - Sons of the American RevolutionScott H. Okuno - Mayo ClinicChristian F. Meyer - Johns Hopkins HospitalGregory M. Cote - Harvard Medical SchoolRashmi Chugh - University of MichiganMohammed M. Milhem - University of IowaAngela C. Hirbe - Washington University in St. LouisAeRang Kim - Children's NationalBrian Turpin - Cincinnati Children's Hospital Medical CenterJoseph G. Pressey - University of AlabamaEva Dombi - National Cancer Institute, Center for Cancer Research, Pediatric Oncology Branch, 10 Center Drive, Building 10, Room 1-3752, Bethesda, MD 20892, USA.Nalini Jayaprakash - National Cancer Institute, Center for Cancer Research, Pediatric Oncology Branch, 10 Center Drive, Building 10, Room 1-3752, Bethesda, MD 20892, USA.Lee J. Helman - National Cancer Institute, Center for Cancer Research, Pediatric Oncology Branch, 10 Center Drive, Building 10, Room 1-3752, Bethesda, MD 20892, USA.Ndidi Onwudiwe - Sons of the American RevolutionKaren Cichowski - Brigham and Women's HospitalJohn P. Perentesis - Cincinnati Children's Hospital Medical Center
- Resource Type
- Journal article
- Publication Details
- Sarcoma, Vol.2019, pp.1-8
- DOI
- 10.1155/2019/7656747
- PMID
- 31427883
- PMCID
- PMC6681622
- NLM abbreviation
- Sarcoma
- ISSN
- 1357-714X
- eISSN
- 1369-1643
- Grant note
- name: Office of the Assistant Secretary of Defense for Health Affairs, award: W81XWH-10-1-0681
- Language
- English
- Date published
- 07/24/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359810702771
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