title: Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study.
abstract: OBJECTIVE
  Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30(+) PTCL.
  
  
  METHODS
  Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches.
  
  
  RESULTS
  After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).
  
  
  CONCLUSIONS
  Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30(+) PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152).
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom. mfanale@mdanderson.org.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Fanale
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Chen
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Illidge
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Dirk
authors.initials: D
authors.lastname: Huebner
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Kennedy
authors.affiliation: Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Steven M. Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY; Andres Forero-Torres, University of Alabama at Birmingham, Birmingham, AL; Nancy L. Bartlett, Washington University School of Medicine, St Louis, MO; Ranjana H. Advani, Stanford University Medical Center, Palo Alto; Robert W. Chen, City of Hope National Medical Center, Duarte, CA; Barbara Pro, Fox Chase Cancer Center, Philadelphia, PA; Dirk Huebner, Takeda Pharmaceuticals International, Cambridge, MA; Dana A. Kennedy, Seattle Genetics, Bothell; Andrei R. Shustov, University of Washington Medical Center, Seattle, WA; Andrew Davies, University of Southampton School of Medicine, Southampton; Tim Illidge, Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000079963:Brentuximab Vedotin; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D017730:Ki-1 Antigen / Q000378:metabolism*; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
chemical_list: D018796:Immunoconjugates; D017730:Ki-1 Antigen; D014750:Vincristine; D000079963:Brentuximab Vedotin; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone