title: Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study.
abstract: The vascular disrupting agent fosbretabulin tromethamine selectively targets pre-existing tumor vasculature, which causes vascular shutdown and leads to cancer cell death and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized antivascular endothelial growth factor monoclonal antibody, might prevent revascularization during and after treatment with a vascular disrupting agent.
  
  
  
  Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or the combination of bevacizumab (15 mg/kg) plus fosbretabulin (60 mg/m(2)) intravenously once every 3 weeks until disease progression or toxicity. Randomization was stratified by disease status (measurable v nonmeasurable), prior bevacizumab, and platinum-free interval. The primary end point was progression-free survival (PFS). The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%.
  
  
  
  The study enrolled 107 patients. Median PFS was 4.8 months for bevacizumab and 7.3 months for bevacizumab plus fosbretabulin (hazard ratio, 0.69; 90% two-sided CI, 0.47 to 1.00; one-sided P = .05). The proportion responding (overall response rate) to bevacizumab was 28.2% among 39 patients with measurable disease and 35.7% among 42 patients treated with the combination. The relative probability of responding was 1.27 (90% CI, 0.74 to 2.17; one-sided P = .24). Adverse events greater than grade 3 were more common in the combination regimen than in bevacizumab only for hypertension (35% v 20%). There was one grade 3 thromboembolic event in the combination arm and one intestinal fistula in the bevacizumab only arm.
  
  
  
  On the basis of the PFS, overall response rate, and tolerability of these two antivascular therapies, further evaluation is warranted for this chemotherapy-free regimen. Fosbretabulin in combination with bevacizumab increases the risk of hypertension.
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX. bradley.monk@chw.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Darus
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Gregory
authors.initials: G
authors.lastname: Sutton
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Lainie P
authors.initials: LP
authors.lastname: Martin
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Schilder
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jai
authors.initials: J
authors.lastname: Balkissoon
authors.affiliation: Bradley J. Monk, University of Arizona Cancer Center at Dignity Health St Joseph's Hospital and Medical Center, Phoenix, AZ; Michael W. Sill, Roswell Park Cancer Institute, Buffalo; Carol Aghajanian, Memorial Sloan Kettering Cancer Center, New York, NY; Joan L. Walker, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Christopher J. Darus, Maine Medical Center, Portland, ME; Gregory Sutton, Washington University School of Medicine, St. Louis, MO; Krishnansu S. Tewari, University of California Irvine Medical Center, Orange; Jai Balkissoon, Pharmaceutical Product Development International, South San Francisco, CA; Lainie P. Martin, Fox Chase Cancer Center, Philadelphia, PA; Jeanne M. Schilder, Indiana University Medical Center, Indianapolis, IN; and Robert L. Coleman, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D013267:Stilbenes; D000068258:Bevacizumab; C058728:fosbretabulin