PittsburghV1, PascalFrancis, Curation, bibRecord, 002244

Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

Identifieur interne : 002244 ( PascalFrancis/Curation ); précédent : 002243; suivant : 002245

Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

Auteurs : Antoni Ribas [États-Unis] ; Richard Kefford [Australie] ; Margaret A. Marshall [États-Unis] ; Cornelis J. A. Punt [Pays-Bas] ; John B. Haanen [Pays-Bas] ; Maribel Marmol [Espagne] ; Claus Garbe [Allemagne] ; Helen Gogas [Grèce] ; Jacob Schachter [Israël] ; Gerald Linette [États-Unis] ; Paul Lorigan [Royaume-Uni] ; Kari L. Kendra [États-Unis] ; Michele Maio [Italie] ; Uwe Trefzer [Allemagne] ; Michael Smylie [Canada] ; Grant A. Mcarthur [Australie] ; Brigitte Dreno [France] ; Paul D. Nathan [Royaume-Uni] ; Jacek Mackiewicz [Pologne] ; John M. Kirkwood [États-Unis] ; Jesus Gomez-Navarro [États-Unis] ; BO HUANG [États-Unis] ; Dmitri Pavlov [États-Unis] ; Axel Hauschild [Allemagne]

Source :

Journal of clinical oncology [ 0732-183X ] ; 2013.

RBID : Pascal:13-0098636

Descripteurs français

Pascal (Inist)
- Essai clinique phase III, Randomisation, Etude comparative, Trémélimumab, Traitement, Homme, Chimiothérapie, Stade avancé, Cancérologie, Mélanome malin, Soin standard.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Advanced stage, Cancerology, Chemotherapy, Comparative study, Human, Malignant melanoma, Phase III trial, Randomization, Treatment, Tremelimumab.

Abstract

Purpose In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage Illc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P= .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

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A14	`12`			`@1 Sheba Medical Centre @2 Tel Hashomer @3 ISR @Z 9 aut.`
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A14	`19`			`@1 Centre Hospitalier Universitaire de Nantes-Hôtel Dieu, Clinique Dermatologique @2 Nantes @3 FRA @Z 17 aut.`
A14	`20`			`@1 Zaklad Diagnostyki i Immunologii Nowotworow Wielkopolskie Centrum Onkologii, University of Medical Sciences @2 Poznan @3 POL @Z 19 aut.`
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C01	`01`		`ENG`	@0 Purpose In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage Illc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P= .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.
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Le document en format XML

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<author><name sortKey="Garbe, Claus" sort="Garbe, Claus" uniqKey="Garbe C" first="Claus" last="Garbe">Claus Garbe</name>
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<author><name sortKey="Gogas, Helen" sort="Gogas, Helen" uniqKey="Gogas H" first="Helen" last="Gogas">Helen Gogas</name>
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<author><name sortKey="Schachter, Jacob" sort="Schachter, Jacob" uniqKey="Schachter J" first="Jacob" last="Schachter">Jacob Schachter</name>
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<author><name sortKey="Linette, Gerald" sort="Linette, Gerald" uniqKey="Linette G" first="Gerald" last="Linette">Gerald Linette</name>
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<author><name sortKey="Lorigan, Paul" sort="Lorigan, Paul" uniqKey="Lorigan P" first="Paul" last="Lorigan">Paul Lorigan</name>
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<author><name sortKey="Kendra, Kari L" sort="Kendra, Kari L" uniqKey="Kendra K" first="Kari L." last="Kendra">Kari L. Kendra</name>
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<author><name sortKey="Maio, Michele" sort="Maio, Michele" uniqKey="Maio M" first="Michele" last="Maio">Michele Maio</name>
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<author><name sortKey="Trefzer, Uwe" sort="Trefzer, Uwe" uniqKey="Trefzer U" first="Uwe" last="Trefzer">Uwe Trefzer</name>
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<author><name sortKey="Smylie, Michael" sort="Smylie, Michael" uniqKey="Smylie M" first="Michael" last="Smylie">Michael Smylie</name>
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<author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
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<author><name sortKey="Dreno, Brigitte" sort="Dreno, Brigitte" uniqKey="Dreno B" first="Brigitte" last="Dreno">Brigitte Dreno</name>
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<author><name sortKey="Nathan, Paul D" sort="Nathan, Paul D" uniqKey="Nathan P" first="Paul D." last="Nathan">Paul D. Nathan</name>
<affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Mount Vernon Hospital</s1>
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<author><name sortKey="Mackiewicz, Jacek" sort="Mackiewicz, Jacek" uniqKey="Mackiewicz J" first="Jacek" last="Mackiewicz">Jacek Mackiewicz</name>
<affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Zaklad Diagnostyki i Immunologii Nowotworow Wielkopolskie Centrum Onkologii, University of Medical Sciences</s1>
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<author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M." last="Kirkwood">John M. Kirkwood</name>
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<author><name sortKey="Gomez Navarro, Jesus" sort="Gomez Navarro, Jesus" uniqKey="Gomez Navarro J" first="Jesus" last="Gomez-Navarro">Jesus Gomez-Navarro</name>
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<author><name sortKey="Bo Huang" sort="Bo Huang" uniqKey="Bo Huang" last="Bo Huang">BO HUANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
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<author><name sortKey="Pavlov, Dmitri" sort="Pavlov, Dmitri" uniqKey="Pavlov D" first="Dmitri" last="Pavlov">Dmitri Pavlov</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Hauschild, Axel" sort="Hauschild, Axel" uniqKey="Hauschild A" first="Axel" last="Hauschild">Axel Hauschild</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>University of Kiel</s1>
<s2>Kiel</s2>
<s3>DEU</s3>
<sZ>24 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">13-0098636</idno>
<date when="2013">2013</date>
<idno type="stanalyst">PASCAL 13-0098636 INIST</idno>
<idno type="RBID">Pascal:13-0098636</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">002677</idno>
<idno type="wicri:Area/PascalFrancis/Curation">002244</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma</title>
<author><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>University of California Los Angeles</s1>
<s2>Los Angeles, CA</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Kefford, Richard" sort="Kefford, Richard" uniqKey="Kefford R" first="Richard" last="Kefford">Richard Kefford</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Westmead Institute for Cancer Research and Melanoma Institute Australia, University of Sydney at Westmead Hospital</s1>
<s2>Sydney, New South Wales</s2>
<s3>AUS</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
<country>Australie</country>
</affiliation>
</author>
<author><name sortKey="Marshall, Margaret A" sort="Marshall, Margaret A" uniqKey="Marshall M" first="Margaret A." last="Marshall">Margaret A. Marshall</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Punt, Cornelis J A" sort="Punt, Cornelis J A" uniqKey="Punt C" first="Cornelis J. A." last="Punt">Cornelis J. A. Punt</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Radboud University Nijmegen Medical Center</s1>
<s2>Nijmegen</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
</affiliation>
</author>
<author><name sortKey="Haanen, John B" sort="Haanen, John B" uniqKey="Haanen J" first="John B." last="Haanen">John B. Haanen</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Netherlands Cancer Institute</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
</affiliation>
</author>
<author><name sortKey="Marmol, Maribel" sort="Marmol, Maribel" uniqKey="Marmol M" first="Maribel" last="Marmol">Maribel Marmol</name>
<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Hospital Clinic of Barcelona</s1>
<s2>Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>Espagne</country>
</affiliation>
</author>
<author><name sortKey="Garbe, Claus" sort="Garbe, Claus" uniqKey="Garbe C" first="Claus" last="Garbe">Claus Garbe</name>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>University Hospital Tübingen</s1>
<s2>Tübingen</s2>
<s3>DEU</s3>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Gogas, Helen" sort="Gogas, Helen" uniqKey="Gogas H" first="Helen" last="Gogas">Helen Gogas</name>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Grèce</country>
</affiliation>
</author>
<author><name sortKey="Schachter, Jacob" sort="Schachter, Jacob" uniqKey="Schachter J" first="Jacob" last="Schachter">Jacob Schachter</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Sheba Medical Centre</s1>
<s2>Tel Hashomer</s2>
<s3>ISR</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Israël</country>
</affiliation>
</author>
<author><name sortKey="Linette, Gerald" sort="Linette, Gerald" uniqKey="Linette G" first="Gerald" last="Linette">Gerald Linette</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Washington University School of Medicine</s1>
<s2>St Louis, MO</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Lorigan, Paul" sort="Lorigan, Paul" uniqKey="Lorigan P" first="Paul" last="Lorigan">Paul Lorigan</name>
<affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Christie Hospital, National Health Service Foundation Trust</s1>
<s2>Manchester</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
</affiliation>
</author>
<author><name sortKey="Kendra, Kari L" sort="Kendra, Kari L" uniqKey="Kendra K" first="Kari L." last="Kendra">Kari L. Kendra</name>
<affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Arthur G. James Cancer Hospital and Richard J. Solve Research Institute</s1>
<s2>Columbus, OH</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Maio, Michele" sort="Maio, Michele" uniqKey="Maio M" first="Michele" last="Maio">Michele Maio</name>
<affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Immunoterapia Oncologica-Azienda Ospedaliera Universitaria Senese</s1>
<s2>Siena</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Trefzer, Uwe" sort="Trefzer, Uwe" uniqKey="Trefzer U" first="Uwe" last="Trefzer">Uwe Trefzer</name>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Skin Cancer Center, Charite Universitatsmedizin Berlin</s1>
<s2>Berlin</s2>
<s3>DEU</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Smylie, Michael" sort="Smylie, Michael" uniqKey="Smylie M" first="Michael" last="Smylie">Michael Smylie</name>
<affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Cross Cancer Institute, University of Alberta</s1>
<s2>Edmonton, Alberta</s2>
<s3>CAN</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Canada</country>
</affiliation>
</author>
<author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Australie</country>
</affiliation>
</author>
<author><name sortKey="Dreno, Brigitte" sort="Dreno, Brigitte" uniqKey="Dreno B" first="Brigitte" last="Dreno">Brigitte Dreno</name>
<affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Centre Hospitalier Universitaire de Nantes-Hôtel Dieu, Clinique Dermatologique</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Nathan, Paul D" sort="Nathan, Paul D" uniqKey="Nathan P" first="Paul D." last="Nathan">Paul D. Nathan</name>
<affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Mount Vernon Hospital</s1>
<s2>Northwood, Middlesex</s2>
<s3>GBR</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
</affiliation>
</author>
<author><name sortKey="Mackiewicz, Jacek" sort="Mackiewicz, Jacek" uniqKey="Mackiewicz J" first="Jacek" last="Mackiewicz">Jacek Mackiewicz</name>
<affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Zaklad Diagnostyki i Immunologii Nowotworow Wielkopolskie Centrum Onkologii, University of Medical Sciences</s1>
<s2>Poznan</s2>
<s3>POL</s3>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Pologne</country>
</affiliation>
</author>
<author><name sortKey="Kirkwood, John M" sort="Kirkwood, John M" uniqKey="Kirkwood J" first="John M." last="Kirkwood">John M. Kirkwood</name>
<affiliation wicri:level="1"><inist:fA14 i1="21"><s1>University of Pittsburgh School of Medicine</s1>
<s2>Pittsburgh, PA</s2>
<s3>USA</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Gomez Navarro, Jesus" sort="Gomez Navarro, Jesus" uniqKey="Gomez Navarro J" first="Jesus" last="Gomez-Navarro">Jesus Gomez-Navarro</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Bo Huang" sort="Bo Huang" uniqKey="Bo Huang" last="Bo Huang">BO HUANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Pavlov, Dmitri" sort="Pavlov, Dmitri" uniqKey="Pavlov D" first="Dmitri" last="Pavlov">Dmitri Pavlov</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Hauschild, Axel" sort="Hauschild, Axel" uniqKey="Hauschild A" first="Axel" last="Hauschild">Axel Hauschild</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>University of Kiel</s1>
<s2>Kiel</s2>
<s3>DEU</s3>
<sZ>24 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of clinical oncology</title>
<title level="j" type="abbreviated">J. clin. oncol.</title>
<idno type="ISSN">0732-183X</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of clinical oncology</title>
<title level="j" type="abbreviated">J. clin. oncol.</title>
<idno type="ISSN">0732-183X</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced stage</term>
<term>Cancerology</term>
<term>Chemotherapy</term>
<term>Comparative study</term>
<term>Human</term>
<term>Malignant melanoma</term>
<term>Phase III trial</term>
<term>Randomization</term>
<term>Treatment</term>
<term>Tremelimumab</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Essai clinique phase III</term>
<term>Randomisation</term>
<term>Etude comparative</term>
<term>Trémélimumab</term>
<term>Traitement</term>
<term>Homme</term>
<term>Chimiothérapie</term>
<term>Stade avancé</term>
<term>Cancérologie</term>
<term>Mélanome malin</term>
<term>Soin standard</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Purpose In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage Illc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P= .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0732-183X</s0>
</fA01>
<fA03 i2="1"><s0>J. clin. oncol.</s0>
</fA03>
<fA05><s2>31</s2>
</fA05>
<fA06><s2>5</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>RIBAS (Antoni)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>KEFFORD (Richard)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>MARSHALL (Margaret A.)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>PUNT (Cornelis J. A.)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>HAANEN (John B.)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>MARMOL (Maribel)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>GARBE (Claus)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>GOGAS (Helen)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>SCHACHTER (Jacob)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>LINETTE (Gerald)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>LORIGAN (Paul)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>KENDRA (Kari L.)</s1>
</fA11>
<fA11 i1="13" i2="1"><s1>MAIO (Michele)</s1>
</fA11>
<fA11 i1="14" i2="1"><s1>TREFZER (Uwe)</s1>
</fA11>
<fA11 i1="15" i2="1"><s1>SMYLIE (Michael)</s1>
</fA11>
<fA11 i1="16" i2="1"><s1>MCARTHUR (Grant A.)</s1>
</fA11>
<fA11 i1="17" i2="1"><s1>DRENO (Brigitte)</s1>
</fA11>
<fA11 i1="18" i2="1"><s1>NATHAN (Paul D.)</s1>
</fA11>
<fA11 i1="19" i2="1"><s1>MACKIEWICZ (Jacek)</s1>
</fA11>
<fA11 i1="20" i2="1"><s1>KIRKWOOD (John M.)</s1>
</fA11>
<fA11 i1="21" i2="1"><s1>GOMEZ-NAVARRO (Jesus)</s1>
</fA11>
<fA11 i1="22" i2="1"><s1>BO HUANG</s1>
</fA11>
<fA11 i1="23" i2="1"><s1>PAVLOV (Dmitri)</s1>
</fA11>
<fA11 i1="24" i2="1"><s1>HAUSCHILD (Axel)</s1>
</fA11>
<fA14 i1="01"><s1>University of California Los Angeles</s1>
<s2>Los Angeles, CA</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Westmead Institute for Cancer Research and Melanoma Institute Australia, University of Sydney at Westmead Hospital</s1>
<s2>Sydney, New South Wales</s2>
<s3>AUS</s3>
<sZ>2 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>16 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Pfizer Global Research and Development</s1>
<s2>Groton, CT</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
<sZ>23 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Radboud University Nijmegen Medical Center</s1>
<s2>Nijmegen</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Netherlands Cancer Institute</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Hospital Clinic of Barcelona</s1>
<s2>Barcelona</s2>
<s3>ESP</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="08"><s1>University Hospital Tübingen</s1>
<s2>Tübingen</s2>
<s3>DEU</s3>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="09"><s1>Skin Cancer Center, Charite Universitatsmedizin Berlin</s1>
<s2>Berlin</s2>
<s3>DEU</s3>
<sZ>14 aut.</sZ>
</fA14>
<fA14 i1="10"><s1>University of Kiel</s1>
<s2>Kiel</s2>
<s3>DEU</s3>
<sZ>24 aut.</sZ>
</fA14>
<fA14 i1="11"><s1>University of Athens</s1>
<s2>Athens</s2>
<s3>GRC</s3>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="12"><s1>Sheba Medical Centre</s1>
<s2>Tel Hashomer</s2>
<s3>ISR</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="13"><s1>Washington University School of Medicine</s1>
<s2>St Louis, MO</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="14"><s1>Christie Hospital, National Health Service Foundation Trust</s1>
<s2>Manchester</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="15"><s1>Mount Vernon Hospital</s1>
<s2>Northwood, Middlesex</s2>
<s3>GBR</s3>
<sZ>18 aut.</sZ>
</fA14>
<fA14 i1="16"><s1>Arthur G. James Cancer Hospital and Richard J. Solve Research Institute</s1>
<s2>Columbus, OH</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="17"><s1>Immunoterapia Oncologica-Azienda Ospedaliera Universitaria Senese</s1>
<s2>Siena</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
</fA14>
<fA14 i1="18"><s1>Cross Cancer Institute, University of Alberta</s1>
<s2>Edmonton, Alberta</s2>
<s3>CAN</s3>
<sZ>15 aut.</sZ>
</fA14>
<fA14 i1="19"><s1>Centre Hospitalier Universitaire de Nantes-Hôtel Dieu, Clinique Dermatologique</s1>
<s2>Nantes</s2>
<s3>FRA</s3>
<sZ>17 aut.</sZ>
</fA14>
<fA14 i1="20"><s1>Zaklad Diagnostyki i Immunologii Nowotworow Wielkopolskie Centrum Onkologii, University of Medical Sciences</s1>
<s2>Poznan</s2>
<s3>POL</s3>
<sZ>19 aut.</sZ>
</fA14>
<fA14 i1="21"><s1>University of Pittsburgh School of Medicine</s1>
<s2>Pittsburgh, PA</s2>
<s3>USA</s3>
<sZ>20 aut.</sZ>
</fA14>
<fA20><s1>616-622</s1>
</fA20>
<fA21><s1>2013</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>20094</s2>
<s5>354000182530890160</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2013 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>13 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>13-0098636</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Journal of clinical oncology</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Purpose In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage Illc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P= .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B04</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B08A</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Essai clinique phase III</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Phase III trial</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Ensayo clínico fase III</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Randomisation</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Randomization</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Aleatorización</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Etude comparative</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Comparative study</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Estudio comparativo</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Trémélimumab</s0>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Tremelimumab</s0>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Tremelimumab</s0>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Traitement</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Treatment</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Tratamiento</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Homme</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Human</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Hombre</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Chimiothérapie</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Chemotherapy</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Quimioterapia</s0>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Stade avancé</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Advanced stage</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Estadio avanzado</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Cancérologie</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Cancerology</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Cancerología</s0>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Mélanome malin</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Malignant melanoma</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Melanoma maligno</s0>
<s5>10</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Soin standard</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s2>NM</s2>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s2>NM</s2>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s2>NM</s2>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Cáncer</s0>
<s2>NM</s2>
</fC07>
<fN21><s1>070</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

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