title: Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial.
abstract: OBJECTIVE
  There is evidence from nonrandomized studies that a proportion of ipilimumab-treated patients with advanced melanoma experience long-term survival. To demonstrate a long-term survival benefit with ipilimumab, we evaluated the 5-year survival rates of patients treated in a randomized, controlled phase III trial.
  
  
  METHODS
  A milestone survival analysis was conducted to capture the 5-year survival rate of treatment-naive patients with advanced melanoma who received ipilimumab in a phase III trial. Patients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or placebo plus dacarbazine (n = 252) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24. A safety analysis was conducted on patients who survived at least 5 years and continued to receive ipilimumab as maintenance therapy.
  
  
  RESULTS
  The 5-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine (P = .002). A plateau in the survival curve began at approximately 3 years. In patients who survived at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events were observed exclusively in the skin.
  
  
  CONCLUSIONS
  The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma.
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY. mmaiocro@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Grob
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Vanna
authors.initials: V
authors.lastname: Chiarion-Sileni
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Tai-Tsang
authors.initials: TT
authors.lastname: Chen
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Marina
authors.initials: M
authors.lastname: Tschaika
authors.affiliation: Michele Maio, University Hospital of Siena, Siena; Vanna Chiarion-Sileni, Veneto Oncology Institute-Istituto Di Ricovero e Cura a Carattere Scientifico, Padova; Alessandro Testori, Istituto Europeo di Oncologia, Milan, Italy; Jean-Jacques Grob, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Hôpital Timone, Marseille; Luc Thomas, Lyon 1 University, Centre Hospitalier Lyon Sud, Pierre Bénite; Caroline Robert, Institute Gustave Roussy, Villejuif, France; Steinar Aamdal, Oslo University Hospital and Radium Hospital, Oslo, Norway; Igor Bondarenko, Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine; Claus Garbe, University Medical Center, Tübingen, Germany; Tai-Tsang Chen and Marina Tschaika, Bristol-Myers Squibb, Wallingford, CT; and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011537:Pruritus / Q000139:chemically induced; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014820:Vitiligo / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D003606:Dacarbazine