title: Ipilimumab in treatment-naive and previously treated patients with metastatic melanoma: retrospective analysis of efficacy and safety data from a phase II trial.
abstract: Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate antitumor T-cell responses. In a phase III trial, ipilimumab monotherapy at 3 mg/kg demonstrated an improvement in overall survival (OS) in patients with previously treated, metastatic melanoma. Here, we conducted a retrospective analysis of efficacy and safety data from a phase II clinical trial in which treatment-naive and previously treated patients with metastatic melanoma received ipilimumab at an investigational dose of 10 mg/kg. Patients were randomized 1:1 to receive oral budesonide or placebo, and ipilimumab at 10 mg/kg every 3 weeks for 4 doses, to determine whether prophylactic budesonide affected the rate of grade ≥2 diarrhea. One hundred fifteen patients were randomized and treated: 62 had received prior systemic therapy for metastatic disease and 53 had not. No efficacy endpoint was affected by budesonide therapy, and the efficacy data were therefore pooled for budesonide and placebo subgroups. Median OS was 30.5 months for treatment-naive patients who received ipilimumab, with survival rates of 69.4%, 62.9%, and 56.9% at 12, 18, and 24 months. In previously treated patients who received ipilimumab, median OS was 13.6 months, with survival rates of 50.0%, 37.7%, and 28.5% at 12, 18, and 24 months. There were no meaningful differences in the number of objective responses or rate of grade ≥2 diarrhea between groups. These retrospective analyses are the first to provide survival data for ipilimumab in treatment-naive and previously treated patients within the same clinical trial.
authors: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA. jat@u.washington.edu
authors: John A
authors: JA
authors: Thompson
authors: Omid
authors: O
authors: Hamid
authors: David
authors: D
authors: Minor
authors: Asim
authors: A
authors: Amin
authors: Ilan G
authors: IG
authors: Ron
authors: Ruggero
authors: R
authors: Ridolfi
authors: Hazem
authors: H
authors: Assi
authors: David
authors: D
authors: Berman
authors: Jonathan
authors: J
authors: Siegel
authors: Jeffrey S
authors: JS
authors: Weber
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage; D060908:CTLA-4 Antigen / Q000276:immunology; D003967:Diarrhea / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D019819:Budesonide