title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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; P = .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; P = .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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. gynbreast@mskcc.org.
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.affiliation: 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.
authors.forename: Austin
authors.initials: A
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.affiliation: 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.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: 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.
authors.forename: Kian
authors.initials: K
authors.lastname: Behbakht
authors.affiliation: 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.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Bakkum-Gamez
authors.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Michael
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D000093542:Gemcitabine