title: Phase II study of MEDI-575, an anti-platelet-derived growth factor-α antibody, in patients with recurrent glioblastoma.
abstract: MEDI-575, an immunoglobulin G2κ monoclonal antibody, selectively binds to platelet-derived growth factor-α receptor (PDGFR-α) with high specificity. This multicenter, single-arm, open-label, phase II study evaluated the efficacy and safety of MEDI-575 in patients with recurrent glioblastoma. Adults with first recurrence of glioblastoma following surgery, temozolomide, and radiation received MEDI-575 25 mg/kg intravenously over 60 min every 21 days until disease progression or unacceptable toxicity. Six-month progression-free survival rate (PFS-6) was the primary end point; secondary measures included response rate, overall survival (OS), and safety/tolerability. PDGFR-α expression was evaluated by immunohistochemistry. Fifty-six patients were enrolled; median age was 56.5 years (range 23-79), 66 % were male, and 66 % were aged ≥65 years. PFS-6 was 15.4 % [90 % confidence interval (CI) 8.1-24.9]. No complete or partial responses were observed; 23 (41.1 %) patients had stable disease as best response. Median PFS was 1.4 months (90 % CI 1.4, 1.8); median OS was 9.7 months (90 % CI 6.5, 11.8). The most common treatment-related adverse events (AEs) were diarrhea (16 %), nausea (13 %), and fatigue (13 %). Twelve (21 %) patients reported grade ≥3 AEs, with hydrocephalus (n = 3), dysphagia (n = 2), and convulsion (n = 2) reported in more than 1 patient. Two patients had treatment-related Grade ≥3 AEs of decreased lymphocyte count and asthenia (n = 1 each). Seven patients (13 %) discontinued MEDI-575 owing to AEs. Labeling of PDGFRα in glioblastoma cells and tumor-associated stromal cells was highly variable, with no correlation with PFS. MEDI-575, although well tolerated, had limited clinical activity in recurrent glioblastoma.
authors.affiliation: Johnnie L. Cochran Jr. Brain Tumor Center, Cedars-Sinai Medical Center, 127 South San Vicente Blvd, Los Angeles, CA, USA. phuphanich@hotmail.com.|Department of Neurology, Division of Neuro-Oncology, Barrow Neurological Institute, 240 West Thomas Road, Suite 400, Phoenix, AZ, 85013, USA. phuphanich@hotmail.com.
authors.forename: Surasak
authors.initials: S
authors.lastname: Phuphanich
authors.affiliation: Northwestern Brain Tumor Institute, Northwestern University, 675 N. St. Clair, Chicago, IL, 60611, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Raizer
authors.affiliation: University of Washington, 1959 NE Pacific St., 8th Floor, Seattle, WA, 98195, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Chamberlain
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Canelos
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Narwal
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Shengyan
authors.initials: S
authors.lastname: Hong
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Miday
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Minal
authors.initials: M
authors.lastname: Nade
authors.affiliation: MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Laubscher
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C000594804:Tovetumab
keywords: Anti-PDGFR-α; Monoclonal antibody; Progression-free survival; Safety; Treatment outcomes