Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study
Identifieur interne : 001926 ( Main/Exploration ); précédent : 001925; suivant : 001927Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study
Auteurs : Martee L. Hensley ; Austin Miller ; David M. O'Malley ; Robert S. Mannel ; Kian Behbakht ; Jamie N. Bakkum-Gamez ; Helen MichaelSource :
- Journal of Clinical Oncology [ 0732-183X ] ; 2015.
Abstract
Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS.
In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs.
In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n = 54) and gemcitabine-docetaxel plus bevacizumab (n = 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12;
The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS.
Url:
DOI: 10.1200/JCO.2014.58.3781
PubMed: 25713428
PubMed Central: 4372854
Affiliations:
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Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Miller, Austin" sort="Miller, Austin" uniqKey="Miller A" first="Austin" last="Miller">Austin Miller</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. 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Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Bakkum Gamez, Jamie N" sort="Bakkum Gamez, Jamie N" uniqKey="Bakkum Gamez J" first="Jamie N." last="Bakkum-Gamez">Jamie N. Bakkum-Gamez</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Michael, Helen" sort="Michael, Helen" uniqKey="Michael H" first="Helen" last="Michael">Helen Michael</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25713428</idno><idno type="pmc">4372854</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854</idno><idno type="RBID">PMC:4372854</idno><idno type="doi">10.1200/JCO.2014.58.3781</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000678</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000678</idno><idno type="wicri:Area/Pmc/Curation">000678</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000678</idno><idno type="wicri:Area/Pmc/Checkpoint">000F31</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000F31</idno><idno type="wicri:Area/Ncbi/Merge">007073</idno><idno type="wicri:Area/Ncbi/Curation">007073</idno><idno type="wicri:Area/Ncbi/Checkpoint">007073</idno><idno type="wicri:doubleKey">0732-183X:2015:Hensley M:randomized:phase:iii</idno><idno type="wicri:Area/Main/Merge">001928</idno><idno type="wicri:Area/Main/Curation">001926</idno><idno type="wicri:Area/Main/Exploration">001926</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study</title><author><name sortKey="Hensley, Martee L" sort="Hensley, Martee L" uniqKey="Hensley M" first="Martee L." last="Hensley">Martee L. Hensley</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Miller, Austin" sort="Miller, Austin" uniqKey="Miller A" first="Austin" last="Miller">Austin Miller</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M." last="O'Malley">David M. O'Malley</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Mannel, Robert S" sort="Mannel, Robert S" uniqKey="Mannel R" first="Robert S." last="Mannel">Robert S. Mannel</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Behbakht, Kian" sort="Behbakht, Kian" uniqKey="Behbakht K" first="Kian" last="Behbakht">Kian Behbakht</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Bakkum Gamez, Jamie N" sort="Bakkum Gamez, Jamie N" uniqKey="Bakkum Gamez J" first="Jamie N." last="Bakkum-Gamez">Jamie N. Bakkum-Gamez</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author><author><name sortKey="Michael, Helen" sort="Michael, Helen" uniqKey="Michael H" first="Helen" last="Michael">Helen Michael</name><affiliation><nlm:aff id="aff1">Martee L. Hensley, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York; Austin Miller, NRG Oncology, Buffalo, NY; David M. O'Malley, The Ohio State University, Columbus, OH; Robert S. Mannel, University of Oklahoma, Oklahoma City, OK; Kian Behbakht, University of Colorado Denver, Aurora, CO; Jamie N. Bakkum-Gamez, Mayo Clinic, Rochester, MN; and Helen Michael, Indiana University School of Medicine, Indianapolis, IN.</nlm:aff><wicri:noCountry code="subfield">IN.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Journal of Clinical Oncology</title><idno type="ISSN">0732-183X</idno><idno type="eISSN">1527-7755</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS.</p></sec><sec><title>Patients and Methods</title><p>In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs.</p></sec><sec><title>Results</title><p>In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n = 54) and gemcitabine-docetaxel plus bevacizumab (n = 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12; <italic>P</italic> = .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; <italic>P</italic> = .81). Objective responses were observed in 17 (31.5%) of 54 patients randomly assigned to gemcitabine-docetaxel plus placebo and 19 (35.8%) of 53 patients randomly assigned to gemcitabine-docetaxel plus bevacizumab. Mean duration of response was 8.6 months for gemcitabine-docetaxel plus placebo versus 8.8 months for gemcitabine-docetaxel plus bevacizumab.</p></sec><sec><title>Conclusion</title><p>The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS.</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bakkum Gamez, Jamie N" sort="Bakkum Gamez, Jamie N" uniqKey="Bakkum Gamez J" first="Jamie N." last="Bakkum-Gamez">Jamie N. Bakkum-Gamez</name><name sortKey="Behbakht, Kian" sort="Behbakht, Kian" uniqKey="Behbakht K" first="Kian" last="Behbakht">Kian Behbakht</name><name sortKey="Hensley, Martee L" sort="Hensley, Martee L" uniqKey="Hensley M" first="Martee L." last="Hensley">Martee L. Hensley</name><name sortKey="Mannel, Robert S" sort="Mannel, Robert S" uniqKey="Mannel R" first="Robert S." last="Mannel">Robert S. Mannel</name><name sortKey="Michael, Helen" sort="Michael, Helen" uniqKey="Michael H" first="Helen" last="Michael">Helen Michael</name><name sortKey="Miller, Austin" sort="Miller, Austin" uniqKey="Miller A" first="Austin" last="Miller">Austin Miller</name><name sortKey="O Malley, David M" sort="O Malley, David M" uniqKey="O Malley D" first="David M." last="O'Malley">David M. O'Malley</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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