Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials
Identifieur interne : 000833 ( Main/Exploration ); précédent : 000832; suivant : 000834Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials
Auteurs : Allan Lipton [États-Unis] ; Karim Fizazi [France] ; Alison T. Stopeck [États-Unis] ; David H. Henry [États-Unis] ; Janet E. Brown [Royaume-Uni] ; Denise A. Yardley [États-Unis] ; Gary E. Richardson [Australie] ; Salvatore Siena [Italie] ; Pablo Maroto [Espagne] ; Michael Clemens [Allemagne] ; Boris Bilynskyy [Ukraine] ; Veena Charu [États-Unis] ; Philippe Beuzeboc [France] ; Michael Rader [États-Unis] ; Maria Viniegra [Argentine] ; Fred Saad [Canada] ; Chunlei Ke [États-Unis] ; Ada Braun [États-Unis] ; Susie Jun [États-Unis]Source :
- European journal of cancer : (1990) [ 0959-8049 ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background: Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies. Methods: Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival. Findings: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21 months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P < 0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate (P = 0.13). Conclusion: Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer.
Affiliations:
- Allemagne, Argentine, Australie, Canada, Espagne, France, Italie, Royaume-Uni, Ukraine, États-Unis
- Arizona, Californie, Catalogne, Lombardie, Pennsylvanie, Tennessee, État de New York, Île-de-France
- Barcelone, Milan, Paris, University Park (Pennsylvanie)
- Université d'État de Pennsylvanie
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials</title><author><name sortKey="Lipton, Allan" sort="Lipton, Allan" uniqKey="Lipton A" first="Allan" last="Lipton">Allan Lipton</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Pennsylvania State University, Milton S. Hershey Medical Center</s1><s2>Hershey, PA</s2><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">University Park (Pennsylvanie)</settlement></placeName><orgName type="university">Université d'État de Pennsylvanie</orgName></affiliation></author><author><name sortKey="Fizazi, Karim" sort="Fizazi, Karim" uniqKey="Fizazi K" first="Karim" last="Fizazi">Karim Fizazi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institut Gustave Roussy, University of Paris Sud</s1><s2>Villejuif</s2><s3>FRA</s3><sZ>2 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>University of Paris Sud</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Stopeck, Alison T" sort="Stopeck, Alison T" uniqKey="Stopeck A" first="Alison T." last="Stopeck">Alison T. Stopeck</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>University of Arizona, Arizona Cancer Center</s1><s2>Tucson, AZ</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Henry, David H" sort="Henry, David H" uniqKey="Henry D" first="David H." last="Henry">David H. Henry</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Joan Karnell Cancer Center at Pennsylvania Hospital</s1><s2>Philadelphia, PA</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Brown, Janet E" sort="Brown, Janet E" uniqKey="Brown J" first="Janet E." last="Brown">Janet E. Brown</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Cancer Research UK Clinical Centre</s1><s2>Leeds</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Clinical Centre</wicri:noRegion></affiliation></author><author><name sortKey="Yardley, Denise A" sort="Yardley, Denise A" uniqKey="Yardley D" first="Denise A." last="Yardley">Denise A. Yardley</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Sarah Cannon Research Institute and Tennessee Oncology, PLLC</s1><s2>Nashville, TN</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Richardson, Gary E" sort="Richardson, Gary E" uniqKey="Richardson G" first="Gary E." last="Richardson">Gary E. Richardson</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Cabrini Hospital</s1><s2>Malvern, Vic</s2><s3>AUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Cabrini Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Siena, Salvatore" sort="Siena, Salvatore" uniqKey="Siena S" first="Salvatore" last="Siena">Salvatore Siena</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Ospedale Niguarda Ca' Granda</s1><s2>Milan</s2><s3>ITA</s3><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Maroto, Pablo" sort="Maroto, Pablo" uniqKey="Maroto P" first="Pablo" last="Maroto">Pablo Maroto</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Hospital de La Santa Creu i Sant Pau</s1><s2>Barcelona</s2><s3>ESP</s3><sZ>9 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Clemens, Michael" sort="Clemens, Michael" uniqKey="Clemens M" first="Michael" last="Clemens">Michael Clemens</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Klinikum Mutterhaus der Borromaeerinnen</s1><s2>Trier</s2><s3>DEU</s3><sZ>10 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Trier</wicri:noRegion><wicri:noRegion>Klinikum Mutterhaus der Borromaeerinnen</wicri:noRegion><wicri:noRegion>Klinikum Mutterhaus der Borromaeerinnen</wicri:noRegion></affiliation></author><author><name sortKey="Bilynskyy, Boris" sort="Bilynskyy, Boris" uniqKey="Bilynskyy B" first="Boris" last="Bilynskyy">Boris Bilynskyy</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Cancer Treatment and Diagnostic Center</s1><s2>Lviv</s2><s3>UKR</s3><sZ>11 aut.</sZ></inist:fA14><country>Ukraine</country><wicri:noRegion>Cancer Treatment and Diagnostic Center</wicri:noRegion></affiliation></author><author><name sortKey="Charu, Veena" sort="Charu, Veena" uniqKey="Charu V" first="Veena" last="Charu">Veena Charu</name><affiliation wicri:level="2"><inist:fA14 i1="12"><s1>Pacific Cancer Medical Center Inc.</s1><s2>Anaheim, CA</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Beuzeboc, Philippe" sort="Beuzeboc, Philippe" uniqKey="Beuzeboc P" first="Philippe" last="Beuzeboc">Philippe Beuzeboc</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>Institut Curie</s1><s2>Paris</s2><s3>FRA</s3><sZ>13 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rader, Michael" sort="Rader, Michael" uniqKey="Rader M" first="Michael" last="Rader">Michael Rader</name><affiliation wicri:level="2"><inist:fA14 i1="14"><s1>Union State Bank Cancer Center, Nyack Hospital</s1><s2>Nyack, NY</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Viniegra, Maria" sort="Viniegra, Maria" uniqKey="Viniegra M" first="Maria" last="Viniegra">Maria Viniegra</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Corporacion Medica de General San Martin</s1><s2>Buenos Aires</s2><s3>ARG</s3><sZ>15 aut.</sZ></inist:fA14><country>Argentine</country><wicri:noRegion>Corporacion Medica de General San Martin</wicri:noRegion></affiliation></author><author><name sortKey="Saad, Fred" sort="Saad, Fred" uniqKey="Saad F" first="Fred" last="Saad">Fred Saad</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>University of Montreal Hospital Center</s1><s2>Montreal, QC</s2><s3>CAN</s3><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Montreal Hospital Center</wicri:noRegion></affiliation></author><author><name sortKey="Ke, Chunlei" sort="Ke, Chunlei" uniqKey="Ke C" first="Chunlei" last="Ke">Chunlei Ke</name><affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Amgen Inc</s1><s2>Thousand Oaks, CA</s2><s3>USA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Braun, Ada" sort="Braun, Ada" uniqKey="Braun A" first="Ada" last="Braun">Ada Braun</name><affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Amgen Inc</s1><s2>Thousand Oaks, CA</s2><s3>USA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 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wicri:step="Checkpoint">000184</idno><idno type="wicri:doubleKey">0959-8049:2012:Lipton A:superiority:of:denosumab</idno><idno type="wicri:Area/Main/Merge">000852</idno><idno type="wicri:Area/Main/Curation">000833</idno><idno type="wicri:Area/Main/Exploration">000833</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials</title><author><name sortKey="Lipton, Allan" sort="Lipton, Allan" uniqKey="Lipton A" first="Allan" last="Lipton">Allan Lipton</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Pennsylvania State University, Milton S. Hershey Medical Center</s1><s2>Hershey, PA</s2><s3>USA</s3><sZ>1 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">University Park (Pennsylvanie)</settlement></placeName><orgName type="university">Université d'État de Pennsylvanie</orgName></affiliation></author><author><name sortKey="Fizazi, Karim" sort="Fizazi, Karim" uniqKey="Fizazi K" first="Karim" last="Fizazi">Karim Fizazi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institut Gustave Roussy, University of Paris Sud</s1><s2>Villejuif</s2><s3>FRA</s3><sZ>2 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>University of Paris Sud</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Stopeck, Alison T" sort="Stopeck, Alison T" uniqKey="Stopeck A" first="Alison T." last="Stopeck">Alison T. Stopeck</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>University of Arizona, Arizona Cancer Center</s1><s2>Tucson, AZ</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Henry, David H" sort="Henry, David H" uniqKey="Henry D" first="David H." last="Henry">David H. Henry</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Joan Karnell Cancer Center at Pennsylvania Hospital</s1><s2>Philadelphia, PA</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Brown, Janet E" sort="Brown, Janet E" uniqKey="Brown J" first="Janet E." last="Brown">Janet E. Brown</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Cancer Research UK Clinical Centre</s1><s2>Leeds</s2><s3>GBR</s3><sZ>5 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Clinical Centre</wicri:noRegion></affiliation></author><author><name sortKey="Yardley, Denise A" sort="Yardley, Denise A" uniqKey="Yardley D" first="Denise A." last="Yardley">Denise A. Yardley</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Sarah Cannon Research Institute and Tennessee Oncology, PLLC</s1><s2>Nashville, TN</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Richardson, Gary E" sort="Richardson, Gary E" uniqKey="Richardson G" first="Gary E." last="Richardson">Gary E. Richardson</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Cabrini Hospital</s1><s2>Malvern, Vic</s2><s3>AUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Cabrini Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Siena, Salvatore" sort="Siena, Salvatore" uniqKey="Siena S" first="Salvatore" last="Siena">Salvatore Siena</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Ospedale Niguarda Ca' Granda</s1><s2>Milan</s2><s3>ITA</s3><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Maroto, Pablo" sort="Maroto, Pablo" uniqKey="Maroto P" first="Pablo" last="Maroto">Pablo Maroto</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Hospital de La Santa Creu i Sant Pau</s1><s2>Barcelona</s2><s3>ESP</s3><sZ>9 aut.</sZ></inist:fA14><country>Espagne</country><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Clemens, Michael" sort="Clemens, Michael" uniqKey="Clemens M" first="Michael" last="Clemens">Michael Clemens</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Klinikum Mutterhaus der Borromaeerinnen</s1><s2>Trier</s2><s3>DEU</s3><sZ>10 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Trier</wicri:noRegion><wicri:noRegion>Klinikum Mutterhaus der Borromaeerinnen</wicri:noRegion><wicri:noRegion>Klinikum Mutterhaus der Borromaeerinnen</wicri:noRegion></affiliation></author><author><name sortKey="Bilynskyy, Boris" sort="Bilynskyy, Boris" uniqKey="Bilynskyy B" first="Boris" last="Bilynskyy">Boris Bilynskyy</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Cancer Treatment and Diagnostic Center</s1><s2>Lviv</s2><s3>UKR</s3><sZ>11 aut.</sZ></inist:fA14><country>Ukraine</country><wicri:noRegion>Cancer Treatment and Diagnostic Center</wicri:noRegion></affiliation></author><author><name sortKey="Charu, Veena" sort="Charu, Veena" uniqKey="Charu V" first="Veena" last="Charu">Veena Charu</name><affiliation wicri:level="2"><inist:fA14 i1="12"><s1>Pacific Cancer Medical Center Inc.</s1><s2>Anaheim, CA</s2><s3>USA</s3><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Beuzeboc, Philippe" sort="Beuzeboc, Philippe" uniqKey="Beuzeboc P" first="Philippe" last="Beuzeboc">Philippe Beuzeboc</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>Institut Curie</s1><s2>Paris</s2><s3>FRA</s3><sZ>13 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rader, Michael" sort="Rader, Michael" uniqKey="Rader M" first="Michael" last="Rader">Michael Rader</name><affiliation wicri:level="2"><inist:fA14 i1="14"><s1>Union State Bank Cancer Center, Nyack Hospital</s1><s2>Nyack, NY</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Viniegra, Maria" sort="Viniegra, Maria" uniqKey="Viniegra M" first="Maria" last="Viniegra">Maria Viniegra</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Corporacion Medica de General San Martin</s1><s2>Buenos Aires</s2><s3>ARG</s3><sZ>15 aut.</sZ></inist:fA14><country>Argentine</country><wicri:noRegion>Corporacion Medica de General San Martin</wicri:noRegion></affiliation></author><author><name sortKey="Saad, Fred" sort="Saad, Fred" uniqKey="Saad F" first="Fred" last="Saad">Fred Saad</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>University of Montreal Hospital Center</s1><s2>Montreal, QC</s2><s3>CAN</s3><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Montreal Hospital Center</wicri:noRegion></affiliation></author><author><name sortKey="Ke, Chunlei" sort="Ke, Chunlei" uniqKey="Ke C" first="Chunlei" last="Ke">Chunlei Ke</name><affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Amgen Inc</s1><s2>Thousand Oaks, CA</s2><s3>USA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Braun, Ada" sort="Braun, Ada" uniqKey="Braun A" first="Ada" last="Braun">Ada Braun</name><affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Amgen Inc</s1><s2>Thousand Oaks, CA</s2><s3>USA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Jun, Susie" sort="Jun, Susie" uniqKey="Jun S" first="Susie" last="Jun">Susie Jun</name><affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Amgen Inc</s1><s2>Thousand Oaks, CA</s2><s3>USA</s3><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">European journal of cancer : (1990)</title><title level="j" type="abbreviated">Eur. j. cancer : (1990)</title><idno type="ISSN">0959-8049</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">European journal of cancer : (1990)</title><title level="j" type="abbreviated">Eur. j. cancer : (1990)</title><idno type="ISSN">0959-8049</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Antiresorptive agent</term><term>Bone metastasis</term><term>Cancerology</term><term>Clinical trial</term><term>Denosumab</term><term>Phase III trial</term><term>Prevention</term><term>Skeleton</term><term>Zoledronic acid</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dénosumab</term><term>Prévention</term><term>Squelette</term><term>Acide zolédronique</term><term>Essai clinique</term><term>Cancérologie</term><term>Essai clinique phase III</term><term>Métastase osseuse</term><term>Antirésorptif</term><term>Anticancéreux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Patients with bone metastases from advanced cancer often experience skeletal-related events (SRE), which cause substantial pain and morbidity. Denosumab, a fully human monoclonal antibody that inhibits RANK Ligand (RANKL), is a novel bone-targeted agent with a distinct mechanism of action relative to the bisphosphonate zoledronic acid, for prevention of SRE. This pre-planned analysis evaluates the efficacy and safety of denosumab versus zoledronic acid across three pivotal studies. Methods: Patient-level data from three identically designed, randomised, double-blind, active-controlled, phase 3 trials of patients with breast cancer, prostate cancer, other solid tumours or multiple myeloma were combined. End-points included time to first SRE, time to first and subsequent (multiple) SRE, adverse events, time to disease progression and overall survival. Findings: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE by a median 8.21 months, reducing the risk of a first SRE by 17% (hazard ratio, 0.83 [95% confidence interval (CI): 0.76-0.90]; P < 0.001). Efficacy was demonstrated for first and multiple events and across patient subgroups (prior SRE status; age). Disease progression and overall survival were similar between the treatments. In contrast to zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status, and was not associated with acute-phase reactions. Hypocalcaemia was more common for denosumab. Osteonecrosis of the jaw occurred at a similar rate (P = 0.13). Conclusion: Denosumab was superior to zoledronic acid in preventing SRE with favourable safety and convenience in patients with bone metastases from advanced cancer.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Argentine</li><li>Australie</li><li>Canada</li><li>Espagne</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>Ukraine</li><li>États-Unis</li></country><region><li>Arizona</li><li>Californie</li><li>Catalogne</li><li>Lombardie</li><li>Pennsylvanie</li><li>Tennessee</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Barcelone</li><li>Milan</li><li>Paris</li><li>University Park (Pennsylvanie)</li></settlement><orgName><li>Université d'État de Pennsylvanie</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Lipton, Allan" sort="Lipton, Allan" uniqKey="Lipton A" first="Allan" last="Lipton">Allan Lipton</name></region><name sortKey="Braun, Ada" sort="Braun, Ada" uniqKey="Braun A" first="Ada" last="Braun">Ada Braun</name><name sortKey="Charu, Veena" sort="Charu, Veena" uniqKey="Charu V" first="Veena" last="Charu">Veena Charu</name><name sortKey="Henry, David H" sort="Henry, David H" uniqKey="Henry D" first="David H." last="Henry">David H. Henry</name><name sortKey="Jun, Susie" sort="Jun, Susie" uniqKey="Jun S" first="Susie" last="Jun">Susie Jun</name><name sortKey="Ke, Chunlei" sort="Ke, Chunlei" uniqKey="Ke C" first="Chunlei" last="Ke">Chunlei Ke</name><name sortKey="Rader, Michael" sort="Rader, Michael" uniqKey="Rader M" first="Michael" last="Rader">Michael Rader</name><name sortKey="Stopeck, Alison T" sort="Stopeck, Alison T" uniqKey="Stopeck A" first="Alison T." last="Stopeck">Alison T. Stopeck</name><name sortKey="Yardley, Denise A" sort="Yardley, Denise A" uniqKey="Yardley D" first="Denise A." last="Yardley">Denise A. Yardley</name></country><country name="France"><noRegion><name sortKey="Fizazi, Karim" sort="Fizazi, Karim" uniqKey="Fizazi K" first="Karim" last="Fizazi">Karim Fizazi</name></noRegion><name sortKey="Beuzeboc, Philippe" sort="Beuzeboc, Philippe" uniqKey="Beuzeboc P" first="Philippe" last="Beuzeboc">Philippe Beuzeboc</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Brown, Janet E" sort="Brown, Janet E" uniqKey="Brown J" first="Janet E." last="Brown">Janet E. Brown</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Richardson, Gary E" sort="Richardson, Gary E" uniqKey="Richardson G" first="Gary E." last="Richardson">Gary E. Richardson</name></noRegion></country><country name="Italie"><region name="Lombardie"><name sortKey="Siena, Salvatore" sort="Siena, Salvatore" uniqKey="Siena S" first="Salvatore" last="Siena">Salvatore Siena</name></region></country><country name="Espagne"><region name="Catalogne"><name sortKey="Maroto, Pablo" sort="Maroto, Pablo" uniqKey="Maroto P" first="Pablo" last="Maroto">Pablo Maroto</name></region></country><country name="Allemagne"><noRegion><name sortKey="Clemens, Michael" sort="Clemens, Michael" uniqKey="Clemens M" first="Michael" last="Clemens">Michael Clemens</name></noRegion></country><country name="Ukraine"><noRegion><name sortKey="Bilynskyy, Boris" sort="Bilynskyy, Boris" uniqKey="Bilynskyy B" first="Boris" last="Bilynskyy">Boris Bilynskyy</name></noRegion></country><country name="Argentine"><noRegion><name sortKey="Viniegra, Maria" sort="Viniegra, Maria" uniqKey="Viniegra M" first="Maria" last="Viniegra">Maria Viniegra</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Saad, Fred" sort="Saad, Fred" uniqKey="Saad F" first="Fred" last="Saad">Fred Saad</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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