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Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.

Identifieur interne : 000500 ( Main/Exploration ); précédent : 000499; suivant : 000501

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.

Auteurs : Tomasz M. Beer [Pays-Bas] ; Eugene D. Kwon [Pays-Bas] ; Charles G. Drake [Pays-Bas] ; Karim Fizazi [Pays-Bas] ; Christopher Logothetis [Pays-Bas] ; Gwenaelle Gravis [Pays-Bas] ; Vinod Ganju [Pays-Bas] ; Jonathan Polikoff [Pays-Bas] ; Fred Saad [Pays-Bas] ; Piotr Humanski [Pays-Bas] ; Josep M. Piulats [Pays-Bas] ; Pablo Gonzalez Mella [Pays-Bas] ; Siobhan S. Ng [Pays-Bas] ; Dirk Jaeger [Pays-Bas] ; Francis X. Parnis [Pays-Bas] ; Fabio A. Franke [Pays-Bas] ; Javier Puente [Pays-Bas] ; Roman Carvajal [Pays-Bas] ; Lisa Sengel V [Pays-Bas] ; M Brent Mchenry [Pays-Bas] ; Arvind Varma [Pays-Bas] ; Alfonsus J. Van Den Eertwegh [Pays-Bas] ; Winald Gerritsen [Pays-Bas]

Source :

RBID : pubmed:28034081

Descripteurs français

English descriptors

Abstract

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

DOI: 10.1200/JCO.2016.69.1584
PubMed: 28034081


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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<name sortKey="Logothetis, Christopher" sort="Logothetis, Christopher" uniqKey="Logothetis C" first="Christopher" last="Logothetis">Christopher Logothetis</name>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<name sortKey="Gravis, Gwenaelle" sort="Gravis, Gwenaelle" uniqKey="Gravis G" first="Gwenaelle" last="Gravis">Gwenaelle Gravis</name>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<name sortKey="Ganju, Vinod" sort="Ganju, Vinod" uniqKey="Ganju V" first="Vinod" last="Ganju">Vinod Ganju</name>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<title xml:lang="en">Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer.</title>
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<name sortKey="Saad, Fred" sort="Saad, Fred" uniqKey="Saad F" first="Fred" last="Saad">Fred Saad</name>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<name sortKey="Van Den Eertwegh, Alfonsus J" sort="Van Den Eertwegh, Alfonsus J" uniqKey="Van Den Eertwegh A" first="Alfonsus J" last="Van Den Eertwegh">Alfonsus J. Van Den Eertwegh</name>
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<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<name sortKey="Gerritsen, Winald" sort="Gerritsen, Winald" uniqKey="Gerritsen W" first="Winald" last="Gerritsen">Winald Gerritsen</name>
<affiliation wicri:level="3">
<nlm:affiliation>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen, the Netherlands.</nlm:affiliation>
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<wicri:regionArea>Tomasz M. Beer, Oregon Health and Science University, Portland, OR; Eugene D. Kwon, Mayo Clinic, Rochester, MN; Charles G. Drake, Johns Hopkins University, Baltimore, MD; Karim Fizazi, University of Paris-Sud, Villejuif; Gwenaelle Gravis, Institut Paoli-Calmettes, Marseille, France; Christopher Logothetis, University of Texas MD Anderson Cancer Center, Houston, TX; Vinod Ganju, Monash University, Melbourne, Victoria; Siobhan S. Ng, St John of God Hospital, Subiaco, Western Australia; Francis X. Parnis, Adelaide Cancer Centre, Adelaide, South Australia, Australia; Jonathan Polikoff, Southern California Permanente Medical Group, San Marcos, CA; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada; Piotr Humanski, Niepubliczny Zaklad Opieki Zdrowotnej Specjalista, Kutno, Poland; Josep M. Piulats, Institut Català d'Oncologia, Barcelona; Javier Puente, Hospital Clínico San Carlos, Madrid, Spain; Pablo Gonzalez Mella, Instituto Oncologico, Viña del Mar; Pablo Gonzalez Mella, Fundación Arturo Lopez Pérez, Santiago, Chile; Dirk Jaeger, University Hospital, Heidelberg, Germany; Fabio A. Franke, Hospital de Caridade de Ijuí, Ijuí, Brazil; Roman Carvajal, Hospital Regional Valentin Gomez Farias, Zapopan, Mexico; Lisa Sengeløv, Herlev Hospital, Herlev, Denmark; M. Brent McHenry, Bristol-Myers Squibb, Wallingford, CT; Arvind Varma, DOCS Inc, New York, NY; Alfonsus J. van den Eertwegh, VU University Medical Center, Amsterdam; and Winald Gerritsen, Radboud University, Nijmegen</wicri:regionArea>
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<series>
<title level="j">Journal of clinical oncology : official journal of the American Society of Clinical Oncology</title>
<idno type="eISSN">1527-7755</idno>
<imprint>
<date when="2017" type="published">2017</date>
</imprint>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antibodies, Monoclonal (adverse effects)</term>
<term>Antibodies, Monoclonal (therapeutic use)</term>
<term>Antineoplastic Agents (adverse effects)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Asymptomatic Diseases</term>
<term>Bone Neoplasms (blood)</term>
<term>Bone Neoplasms (drug therapy)</term>
<term>Bone Neoplasms (secondary)</term>
<term>Diarrhea (chemically induced)</term>
<term>Disease-Free Survival</term>
<term>Double-Blind Method</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Prostate-Specific Antigen (blood)</term>
<term>Prostatic Neoplasms, Castration-Resistant (blood)</term>
<term>Prostatic Neoplasms, Castration-Resistant (drug therapy)</term>
<term>Prostatic Neoplasms, Castration-Resistant (pathology)</term>
<term>Survival Rate</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Anticorps monoclonaux (effets indésirables)</term>
<term>Anticorps monoclonaux (usage thérapeutique)</term>
<term>Antigène spécifique de la prostate (sang)</term>
<term>Antinéoplasiques (effets indésirables)</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Diarrhée ()</term>
<term>Humains</term>
<term>Maladies asymptomatiques</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Taux de survie</term>
<term>Tumeurs osseuses (sang)</term>
<term>Tumeurs osseuses (secondaire)</term>
<term>Tumeurs osseuses (traitement médicamenteux)</term>
<term>Tumeurs prostatiques résistantes à la castration (anatomopathologie)</term>
<term>Tumeurs prostatiques résistantes à la castration (sang)</term>
<term>Tumeurs prostatiques résistantes à la castration (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en">
<term>Antibodies, Monoclonal</term>
<term>Antineoplastic Agents</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Prostate-Specific Antigen</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Antibodies, Monoclonal</term>
<term>Antineoplastic Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Tumeurs prostatiques résistantes à la castration</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en">
<term>Bone Neoplasms</term>
<term>Prostatic Neoplasms, Castration-Resistant</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en">
<term>Diarrhea</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Bone Neoplasms</term>
<term>Prostatic Neoplasms, Castration-Resistant</term>
</keywords>
<keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr">
<term>Anticorps monoclonaux</term>
<term>Antinéoplasiques</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Prostatic Neoplasms, Castration-Resistant</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Antigène spécifique de la prostate</term>
<term>Tumeurs osseuses</term>
<term>Tumeurs prostatiques résistantes à la castration</term>
</keywords>
<keywords scheme="MESH" qualifier="secondaire" xml:lang="fr">
<term>Tumeurs osseuses</term>
</keywords>
<keywords scheme="MESH" qualifier="secondary" xml:lang="en">
<term>Bone Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Tumeurs osseuses</term>
<term>Tumeurs prostatiques résistantes à la castration</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Anticorps monoclonaux</term>
<term>Antinéoplasiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Asymptomatic Diseases</term>
<term>Disease-Free Survival</term>
<term>Double-Blind Method</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Survival Rate</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Diarrhée</term>
<term>Humains</term>
<term>Maladies asymptomatiques</term>
<term>Mâle</term>
<term>Méthode en double aveugle</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie sans rechute</term>
<term>Taux de survie</term>
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<front>
<div type="abstract" xml:lang="en">Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.</div>
</front>
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<li>Pays-Bas</li>
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<name sortKey="Carvajal, Roman" sort="Carvajal, Roman" uniqKey="Carvajal R" first="Roman" last="Carvajal">Roman Carvajal</name>
<name sortKey="Drake, Charles G" sort="Drake, Charles G" uniqKey="Drake C" first="Charles G" last="Drake">Charles G. Drake</name>
<name sortKey="Fizazi, Karim" sort="Fizazi, Karim" uniqKey="Fizazi K" first="Karim" last="Fizazi">Karim Fizazi</name>
<name sortKey="Franke, Fabio A" sort="Franke, Fabio A" uniqKey="Franke F" first="Fabio A" last="Franke">Fabio A. Franke</name>
<name sortKey="Ganju, Vinod" sort="Ganju, Vinod" uniqKey="Ganju V" first="Vinod" last="Ganju">Vinod Ganju</name>
<name sortKey="Gerritsen, Winald" sort="Gerritsen, Winald" uniqKey="Gerritsen W" first="Winald" last="Gerritsen">Winald Gerritsen</name>
<name sortKey="Gonzalez Mella, Pablo" sort="Gonzalez Mella, Pablo" uniqKey="Gonzalez Mella P" first="Pablo" last="Gonzalez Mella">Pablo Gonzalez Mella</name>
<name sortKey="Gravis, Gwenaelle" sort="Gravis, Gwenaelle" uniqKey="Gravis G" first="Gwenaelle" last="Gravis">Gwenaelle Gravis</name>
<name sortKey="Humanski, Piotr" sort="Humanski, Piotr" uniqKey="Humanski P" first="Piotr" last="Humanski">Piotr Humanski</name>
<name sortKey="Jaeger, Dirk" sort="Jaeger, Dirk" uniqKey="Jaeger D" first="Dirk" last="Jaeger">Dirk Jaeger</name>
<name sortKey="Kwon, Eugene D" sort="Kwon, Eugene D" uniqKey="Kwon E" first="Eugene D" last="Kwon">Eugene D. Kwon</name>
<name sortKey="Logothetis, Christopher" sort="Logothetis, Christopher" uniqKey="Logothetis C" first="Christopher" last="Logothetis">Christopher Logothetis</name>
<name sortKey="Mchenry, M Brent" sort="Mchenry, M Brent" uniqKey="Mchenry M" first="M Brent" last="Mchenry">M Brent Mchenry</name>
<name sortKey="Ng, Siobhan S" sort="Ng, Siobhan S" uniqKey="Ng S" first="Siobhan S" last="Ng">Siobhan S. Ng</name>
<name sortKey="Parnis, Francis X" sort="Parnis, Francis X" uniqKey="Parnis F" first="Francis X" last="Parnis">Francis X. Parnis</name>
<name sortKey="Piulats, Josep M" sort="Piulats, Josep M" uniqKey="Piulats J" first="Josep M" last="Piulats">Josep M. Piulats</name>
<name sortKey="Polikoff, Jonathan" sort="Polikoff, Jonathan" uniqKey="Polikoff J" first="Jonathan" last="Polikoff">Jonathan Polikoff</name>
<name sortKey="Puente, Javier" sort="Puente, Javier" uniqKey="Puente J" first="Javier" last="Puente">Javier Puente</name>
<name sortKey="Saad, Fred" sort="Saad, Fred" uniqKey="Saad F" first="Fred" last="Saad">Fred Saad</name>
<name sortKey="Sengel V, Lisa" sort="Sengel V, Lisa" uniqKey="Sengel V L" first="Lisa" last="Sengel V">Lisa Sengel V</name>
<name sortKey="Van Den Eertwegh, Alfonsus J" sort="Van Den Eertwegh, Alfonsus J" uniqKey="Van Den Eertwegh A" first="Alfonsus J" last="Van Den Eertwegh">Alfonsus J. Van Den Eertwegh</name>
<name sortKey="Varma, Arvind" sort="Varma, Arvind" uniqKey="Varma A" first="Arvind" last="Varma">Arvind Varma</name>
</country>
</tree>
</affiliations>
</record>

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