A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma

Kent C. Shih, Sajeel Chowdhary, Paul Rosenblatt, Alva Weir, Gregg C. Shepard, Jeffrey T. Williams, Mythili Shastry, Howard A. Burris, John D. Hainsworth

Research output: Contribution to journalArticle

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Abstract

Meningiomas that progress after standard therapies are challenging with limited effective chemotherapy options. This phase II trial evaluated the efficacy of everolimus plus bevacizumab in patients with recurrent, progressive meningioma after treatment with surgical resection and local radiotherapy when appropriate. Patients with recurrent meningioma (WHO grade I, II, or III) following standard treatments with surgical resection and radiotherapy received bevacizumab (10 mg/kg IV days 1 and 15) and everolimus (10 mg PO daily) each 28 day cycle. Evaluation of response occurred every 2 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, overall survival and safety. Seventeen patients with a median age of 59 years (29–84) received study treatment. WHO grades at study entry included: I, 5 (29 %); II, 7 (41 %); III, 4 (24 %); unknown, 1 (6 %). Patients received a median of 8 cycles (1–37); all patients are off study treatment. A best response of SD was observed in 15 patients (88 %), and 6 patients had SD for >12 months. Overall median PFS was 22 months (95 % CI 4.5–26.8) and was greater for patients with WHO grade II and III compared to grade I tumors (22.0 months vs 17.5 months). Four patients discontinued treatment due to toxicity (proteinuria, 2; colitis, 1, thrombocytopenia, 1). However, other grade 3 toxicity was uncommon, and no patient had grade 4 toxicity. The combination of everolimus and bevacizumab was well-tolerated, and produced stable disease in 88 % of patients; the median duration of disease stabilization of 10 months (2–29). The median PFS from this prospective trial was similar to previous retrospective reports of bevacizumab in the treatment of recurrent meningioma.

Original languageEnglish (US)
Pages (from-to)281-288
Number of pages8
JournalJournal of Neuro-Oncology
Volume129
Issue number2
DOIs
StatePublished - Sep 1 2016

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Meningioma
Therapeutics
Disease-Free Survival
Bevacizumab
Everolimus
Radiotherapy
Colitis
Proteinuria
Survival Rate
Safety
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma. / Shih, Kent C.; Chowdhary, Sajeel; Rosenblatt, Paul; Weir, Alva; Shepard, Gregg C.; Williams, Jeffrey T.; Shastry, Mythili; Burris, Howard A.; Hainsworth, John D.

In: Journal of Neuro-Oncology, Vol. 129, No. 2, 01.09.2016, p. 281-288.

Research output: Contribution to journalArticle

Shih, KC, Chowdhary, S, Rosenblatt, P, Weir, A, Shepard, GC, Williams, JT, Shastry, M, Burris, HA & Hainsworth, JD 2016, 'A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma', Journal of Neuro-Oncology, vol. 129, no. 2, pp. 281-288. https://doi.org/10.1007/s11060-016-2172-3
Shih, Kent C. ; Chowdhary, Sajeel ; Rosenblatt, Paul ; Weir, Alva ; Shepard, Gregg C. ; Williams, Jeffrey T. ; Shastry, Mythili ; Burris, Howard A. ; Hainsworth, John D. / A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma. In: Journal of Neuro-Oncology. 2016 ; Vol. 129, No. 2. pp. 281-288.
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