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)

Brigitte C. Widemann, Yao Lu, Denise Reinke, Scott H. Okuno, Christian F. Meyer, Gregory M. Cote, Rashmi Chugh, Mohammed M. Milhem, Angela C. Hirbe, Aerang Kim, Brian Turpin, Joseph G. Pressey, Eva Dombi, Nalini Jayaprakash, Lee J. Helman, Ndidi Onwudiwe, Karen Cichowski, John P. Perentesis

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article number7656747
JournalSarcoma
Volume2019
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of '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)'. Together they form a unique fingerprint.

  • Cite this

    Widemann, B. C., Lu, Y., Reinke, D., Okuno, S. H., Meyer, C. F., Cote, G. M., Chugh, R., Milhem, M. M., Hirbe, A. C., Kim, A., Turpin, B., Pressey, J. G., Dombi, E., Jayaprakash, N., Helman, L. J., Onwudiwe, N., Cichowski, K., & Perentesis, J. P. (2019). 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, 2019, [7656747]. https://doi.org/10.1155/2019/7656747