Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Identifieur interne : 003F88 ( Main/Exploration ); précédent : 003F87; suivant : 003F89Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Auteurs : Thomas E. Hutson [États-Unis] ; Bernard Escudier [France] ; Emilio Esteban [Espagne] ; Georg A. Bjarnason [Canada] ; HO YEONG LIM [Corée du Sud] ; Kenneth B. Pittman [Australie] ; Peggy Senico [États-Unis] ; Andreas Niethammer [États-Unis] ; DONGRUI RAY LU [États-Unis] ; Subramanian Hariharan [États-Unis] ; Robert J. Motzer [États-Unis]Source :
- Journal of clinical oncology [ 0732-183X ] ; 2014.
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Abstract
Purpose This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non-clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points. Results Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% Cl, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% Cl, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies. Conclusion In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.
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Motzer</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Pfizer; Memorial Sloan-Kettering Cancer Center</s1><s2>New York, NY</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pfizer; Memorial Sloan-Kettering Cancer Center</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">14-0086449</idno><date when="2014">2014</date><idno type="stanalyst">PASCAL 14-0086449 INIST</idno><idno type="RBID">Pascal:14-0086449</idno><idno type="wicri:Area/PascalFrancis/Corpus">000504</idno><idno type="wicri:Area/PascalFrancis/Curation">005957</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000123</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000123</idno><idno type="wicri:doubleKey">0732-183X:2014:Hutson T:randomized:phase:iii</idno><idno type="wicri:Area/Main/Merge">004047</idno><idno type="wicri:Area/Main/Curation">003F88</idno><idno type="wicri:Area/Main/Exploration">003F88</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma</title><author><name sortKey="Hutson, Thomas E" sort="Hutson, Thomas E" uniqKey="Hutson T" first="Thomas E." last="Hutson">Thomas E. Hutson</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Charles A. Sammons Cancer Center, Baylor University Medical Center</s1><s2>Dallas, TX</s2><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Dallas, TX</wicri:noRegion></affiliation></author><author><name sortKey="Escudier, Bernard" sort="Escudier, Bernard" uniqKey="Escudier B" first="Bernard" last="Escudier">Bernard Escudier</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institut Gustave Roussy</s1><s2>Villejuif</s2><s3>FRA</s3><sZ>2 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Institut Gustave Roussy</wicri:noRegion><wicri:noRegion>Institut Gustave Roussy</wicri:noRegion></affiliation></author><author><name sortKey="Esteban, Emilio" sort="Esteban, Emilio" uniqKey="Esteban E" first="Emilio" last="Esteban">Emilio Esteban</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Hospital Universitario Central de Asturias</s1><s2>Oviedo, Asturias</s2><s3>ESP</s3><sZ>3 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>Hospital Universitario Central de Asturias</wicri:noRegion></affiliation></author><author><name sortKey="Bjarnason, Georg A" sort="Bjarnason, Georg A" uniqKey="Bjarnason G" first="Georg A." last="Bjarnason">Georg A. Bjarnason</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sunnybrook Odette Cancer Centre</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Sunnybrook Odette Cancer Centre</wicri:noRegion></affiliation></author><author><name sortKey="Ho Yeong Lim" sort="Ho Yeong Lim" uniqKey="Ho Yeong Lim" last="Ho Yeong Lim">HO YEONG LIM</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Samsung Medical Center</s1><s2>Seoul</s2><s3>KOR</s3><sZ>5 aut.</sZ></inist:fA14><country>Corée du Sud</country><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Pittman, Kenneth B" sort="Pittman, Kenneth B" uniqKey="Pittman K" first="Kenneth B." last="Pittman">Kenneth B. Pittman</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>The Queen Elizabeth Hospital, Woodville South</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Senico, Peggy" sort="Senico, Peggy" uniqKey="Senico P" first="Peggy" last="Senico">Peggy Senico</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Pfizer, Collegeville</s1><s2>PA</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>PA</wicri:noRegion></affiliation></author><author><name sortKey="Niethammer, Andreas" sort="Niethammer, Andreas" uniqKey="Niethammer A" first="Andreas" last="Niethammer">Andreas Niethammer</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Pfizer</s1><s2>La Jolla, CA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pfizer</wicri:noRegion></affiliation></author><author><name sortKey="Dongrui Ray Lu" sort="Dongrui Ray Lu" uniqKey="Dongrui Ray Lu" last="Dongrui Ray Lu">DONGRUI RAY LU</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Pfizer</s1><s2>La Jolla, CA</s2><s3>USA</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pfizer</wicri:noRegion></affiliation></author><author><name sortKey="Hariharan, Subramanian" sort="Hariharan, Subramanian" uniqKey="Hariharan S" first="Subramanian" last="Hariharan">Subramanian Hariharan</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Pfizer; Memorial Sloan-Kettering Cancer Center</s1><s2>New York, NY</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pfizer; Memorial Sloan-Kettering Cancer Center</wicri:noRegion></affiliation></author><author><name sortKey="Motzer, Robert J" sort="Motzer, Robert J" uniqKey="Motzer R" first="Robert J." last="Motzer">Robert J. Motzer</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Pfizer; Memorial Sloan-Kettering Cancer Center</s1><s2>New York, NY</s2><s3>USA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pfizer; Memorial Sloan-Kettering Cancer Center</wicri:noRegion></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="2014">2014</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>Antiangiogenic agent</term><term>Antineoplastic agent</term><term>Cancerology</term><term>Carcinoma</term><term>Chemotherapy</term><term>Clinical trial</term><term>Comparative study</term><term>Grawitz tumor</term><term>Human</term><term>Immunosuppressive agent</term><term>Kidney cancer</term><term>Metastasis</term><term>Phase III trial</term><term>Randomization</term><term>Second line treatment</term><term>Sorafenib</term><term>Sunitinib</term><term>Temsirolimus</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Essai clinique phase III</term><term>Essai clinique</term><term>Randomisation</term><term>Temsirolimus</term><term>Etude comparative</term><term>Sunitinib</term><term>Chimiothérapie</term><term>Homme</term><term>Stade avancé</term><term>Sorafénib</term><term>Métastase</term><term>Hypernéphrome</term><term>Traitement de deuxième intention</term><term>Cancer rein</term><term>Cancérologie</term><term>Anticancéreux</term><term>Immunodépresseur</term><term>Antiangiogénique</term><term>Carcinome</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 This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non-clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points. Results Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% Cl, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% Cl, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies. Conclusion In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Corée du Sud</li><li>Espagne</li><li>France</li><li>États-Unis</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Hutson, Thomas E" sort="Hutson, Thomas E" uniqKey="Hutson T" first="Thomas E." last="Hutson">Thomas E. Hutson</name></noRegion><name sortKey="Dongrui Ray Lu" sort="Dongrui Ray Lu" uniqKey="Dongrui Ray Lu" last="Dongrui Ray Lu">DONGRUI RAY LU</name><name sortKey="Hariharan, Subramanian" sort="Hariharan, Subramanian" uniqKey="Hariharan S" first="Subramanian" last="Hariharan">Subramanian Hariharan</name><name sortKey="Motzer, Robert J" sort="Motzer, Robert J" uniqKey="Motzer R" first="Robert J." last="Motzer">Robert J. Motzer</name><name sortKey="Niethammer, Andreas" sort="Niethammer, Andreas" uniqKey="Niethammer A" first="Andreas" last="Niethammer">Andreas Niethammer</name><name sortKey="Senico, Peggy" sort="Senico, Peggy" uniqKey="Senico P" first="Peggy" last="Senico">Peggy Senico</name></country><country name="France"><noRegion><name sortKey="Escudier, Bernard" sort="Escudier, Bernard" uniqKey="Escudier B" first="Bernard" last="Escudier">Bernard Escudier</name></noRegion></country><country name="Espagne"><noRegion><name sortKey="Esteban, Emilio" sort="Esteban, Emilio" uniqKey="Esteban E" first="Emilio" last="Esteban">Emilio Esteban</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Bjarnason, Georg A" sort="Bjarnason, Georg A" uniqKey="Bjarnason G" first="Georg A." last="Bjarnason">Georg A. Bjarnason</name></noRegion></country><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Ho Yeong Lim" sort="Ho Yeong Lim" uniqKey="Ho Yeong Lim" last="Ho Yeong Lim">HO YEONG LIM</name></region></country><country name="Australie"><noRegion><name sortKey="Pittman, Kenneth B" sort="Pittman, Kenneth B" uniqKey="Pittman K" first="Kenneth B." last="Pittman">Kenneth B. Pittman</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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