title: Ipilimumab and Bevacizumab in Glioblastoma.
abstract: The median survival in glioblastoma is just over a year, with no standard second-line therapy. Ipilimumab is an immune checkpoint inhibitor that activates the anti-tumour immune response by cytotoxic T-lymphocyte antigen-4 blockade. There is significant evidence supporting its role in the treatment of malignant melanoma, including in patients with brain metastases. The addition of the anti-angiogenesis agent, bevacizumab, seems to offer additional benefit and limit the immune-related side-effects of ipilimumab in melanoma. To date there have been no clinical trials investigating this combination in glioblastoma. In this single practice case series, 20 patients with glioblastoma were consented for and treated with ipilimumab and bevacizumab in combination. Safety, tolerability and the response to treatment were reviewed for all patients. Three patients were treated after palliative first-line radiotherapy, one patient after first-line chemoradiation and 16 patients were treated with recurrent disease. Sixty-five per cent of patients completed four cycles of 3 weekly ipilimumab therapy, administered with 2 weekly bevacizumab. Radiographic responses for patients with recurrent disease were evaluated by Response Assessment in Neuro-oncology (RANO) criteria; 31% of patients showed a partial response, 31% had stable disease and 38% had disease progression. The treatment combination was well tolerated, with treatment terminated before completion due to adverse events in two patients. Autoimmune toxicity was manageable with systemic corticosteroid therapy. Ipilimumab and bevacizumab in combination show promising activity with a predictable and manageable toxicity profile, warranting further clinical studies.
authors.affiliation: UCL Cancer Institute, University College London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Carter
authors.affiliation: University College London Hospital, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Shaw
authors.affiliation: Harley Street at University College Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cohn-Brown
authors.affiliation: UCL Cancer Institute, University College London, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Chester
authors.affiliation: University College London Hospital, London, UK; Mount Vernon Cancer Centre, Northwood, Middlesex, UK. Electronic address: paul.mulholland@nhs.net.
authors.forename: P
authors.initials: P
authors.lastname: Mulholland
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D012878:Skin Neoplasms; D016896:Treatment Outcome; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074324:Ipilimumab; D000068258:Bevacizumab
keywords: Bevacizumab; glioblastoma; high grade glioma; immunotherapy; ipilimumab