title: Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma.
abstract: BACKGROUND
  Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG).
  
  
  METHODS
  Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study.
  
  
  RESULTS
  At interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5 months (range, 3-9 months), and median overall survival (OS) was 9 months (range, 6-19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was 7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27 months).
  
  
  CONCLUSIONS
  This phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort.
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Eudocia Q
authors.initials: EQ
authors.lastname: Lee
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Jan
authors.initials: J
authors.lastname: Drappatz
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Sean A
authors.initials: SA
authors.lastname: Grimm
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Norden
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Nayak
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Mikael L
authors.initials: ML
authors.lastname: Rinne
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Chi
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Kelly
authors.initials: K
authors.lastname: Hempfling
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Christine
authors.initials: C
authors.lastname: McCluskey
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Katrina H
authors.initials: KH
authors.lastname: Smith
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gaffey
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Brendan
authors.initials: B
authors.lastname: Wrigley
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.affiliation: Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts (E.Q.L., D.A.R., A.D.N., L.N., R.B., M.L.R., K.H., C.M., K.H.S., S.C.G., B.W., K.L.L., P.Y.W.); University of Virginia, Charlottesville, Virginia (D.S.); University of Pittsburgh, Pittsburgh, Pennsylvania (J.D.); Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (A.S.C., T,T.B., A.M.); Central DuPage Hospital, Warrenville, Illinois (S.A.G.); Northwestern University, Chicago, Illinois (J.J.R.).
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077767:Panobinostat; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000068258:Bevacizumab; D000077767:Panobinostat
keywords: anaplastic glioma; antiangiogenesis,; bevacizumab; glioblastoma; panobinostat