title: Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies.
abstract: BACKGROUND
  This report provides a survival update at a follow-up of >5 years (5.5-6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported.
  
  
  METHODS
  Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025.
  
  
  RESULTS
  Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%-16.5%, and 15.5%-28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%-49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively.
  
  
  CONCLUSIONS
  At a follow-up of 5-6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS.
  
  
  BACKGROUND
  NCT00162123.
authors.affiliation: Department of Dermatology, APHP, CIC, U976 Hôpital Saint-Louis University Paris Diderot, Paris, France. Electronic address: celeste.lebbe@sls.aphp.fr.
authors.forename: C
authors.initials: C
authors.lastname: Lebbé
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Weber
authors.affiliation: Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Maio
authors.affiliation: Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Neyns
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Harmankaya
authors.affiliation: Melanoma Therapeutics, Translational Research and Immunotherapy, The Angeles Clinic and Research Institute, Los Angeles.
authors.forename: O
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Los Angeles Skin Cancer Institute at Beverly Hills Cancer Center, Beverly Hills.
authors.forename: S J
authors.initials: SJ
authors.lastname: O'Day
authors.affiliation: Global Clinical Research.
authors.forename: C
authors.initials: C
authors.lastname: Konto
authors.affiliation: Global Clinical Research.
authors.forename: L
authors.initials: L
authors.lastname: Cykowski
authors.affiliation: Global Biometric Sciences, Bristol-Myers Squibb Company, Wallingford.
authors.forename: M B
authors.initials: MB
authors.lastname: McHenry
authors.affiliation: Ludwig Center for Cancer Immunotherapy, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab
keywords: advanced melanoma; cytotoxic T-lymphocyte antigen-4; immunotherapy; ipilimumab; long-term survival; survival rate