PMID- 30617130
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20200912
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 25
IP  - 6
DP  - 2019 Mar 15
TI  - Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly 
      Diagnosed Stage III or IV Hodgkin Lymphoma.
PG  - 1718-1726
LID - 10.1158/1078-0432.CCR-18-2435 [doi]
AB  - PURPOSE: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 
      study treated in North America (NA). PATIENTS AND METHODS: ECHELON-1 is a global, 
      open-label, randomized phase III study comparing doxorubicin, vinblastine, and 
      dacarbazine in combination with brentuximab vedotin (A+AVD) versus ABVD (AVD + 
      bleomycin) as first-line therapy in subjects with stage III or IV classical 
      Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive 
      A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 
      cycles. RESULTS: The NA subgroup consisted of 497 subjects in the A+AVD (n = 250) 
      and ABVD (n = 247) arms. Similar to the primary analysis based on the 
      intent-to-treat population, the primary endpoint [modified progression-free 
      survival (PFS) per independent review] demonstrated an improvement among subjects 
      who received A+AVD compared with ABVD (HR = 0.60; P = 0.012). For PFS, the risk 
      of progression or death was also reduced (HR = 0.50; P = 0.002). Subsequent 
      anticancer therapies were lower in the A+AVD arm. Grade 3 or 4 adverse events 
      (AEs) were more common, but there were fewer study discontinuations due to AEs in 
      the A+AVD arm as compared with ABVD. Noted differences between arms included 
      higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% 
      vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated 
      with A+AVD versus ABVD. CONCLUSIONS: The efficacy benefit and manageable toxicity 
      profile observed in the NA subgroup of ECHELON-1 support A+AVD as a frontline 
      treatment option for patients with stage III or IV cHL.
CI  - (c)2019 American Association for Cancer Research.
FAU - Ramchandren, Radhakrishnan
AU  - Ramchandren R
AD  - Department of Hematology/Oncology, Barbara Ann Karmanos Cancer Center, Detroit, 
      Michigan. RRamchandren@utmck.edu.
FAU - Advani, Ranjana H
AU  - Advani RH
AD  - Department of Medicine, Stanford University, Palo Alto, California.
FAU - Ansell, Stephen M
AU  - Ansell SM
AD  - Division of Hematology, Mayo Clinic, Rochester, Minnesota.
FAU - Bartlett, Nancy L
AU  - Bartlett NL
AD  - Division of Oncology, Siteman Cancer Center, Washington University School of 
      Medicine, St. Louis, Missouri.
FAU - Chen, Robert
AU  - Chen R
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California.
FAU - Connors, Joseph M
AU  - Connors JM
AUID- ORCID: 0000-0002-1361-7531
AD  - University of British Columbia and the Department of Medical Oncology, British 
      Columbia Cancer Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada.
FAU - Feldman, Tatyana
AU  - Feldman T
AD  - John Theurer Cancer Centre, Hackensack University Medical Center, Hackensack, New 
      Jersey.
FAU - Forero-Torres, Andres
AU  - Forero-Torres A
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
FAU - Friedberg, Jonathan W
AU  - Friedberg JW
AD  - James P Wilmot Cancer Institute, University of Rochester Medical Center, 
      Rochester, New York.
FAU - Gopal, Ajay K
AU  - Gopal AK
AUID- ORCID: 0000-0003-3023-6834
AD  - Fred Hutchinson Cancer Research Center, University of Washington, Seattle, 
      Washington.
FAU - Gordon, Leo I
AU  - Gordon LI
AUID- ORCID: 0000-0003-1666-7064
AD  - Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, 
      Illinois.
FAU - Kuruvilla, John
AU  - Kuruvilla J
AD  - Division of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, 
      Ontario, Canada.
FAU - Savage, Kerry J
AU  - Savage KJ
AD  - University of British Columbia and the Department of Medical Oncology, British 
      Columbia Cancer Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada.
FAU - Younes, Anas
AU  - Younes A
AD  - Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 
      New York, New York.
FAU - Engley, Gerald
AU  - Engley G
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Manley, Thomas J
AU  - Manley TJ
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Fenton, Keenan
AU  - Fenton K
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Straus, David J
AU  - Straus DJ
AD  - Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 
      New York, New York.
LA  - eng
SI  - ClinicalTrials.gov/NCT01712490
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190107
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 11056-06-7 (Bleomycin)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - 7XL5ISS668 (Brentuximab Vedotin)
RN  - 80168379AG (Doxorubicin)
RN  - ABVD protocol
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Bleomycin/administration & dosage/adverse effects
MH  - Brentuximab Vedotin/*administration & dosage/adverse effects
MH  - Canada
MH  - Chemotherapy-Induced Febrile Neutropenia/epidemiology/etiology
MH  - Dacarbazine/administration & dosage/adverse effects
MH  - Doxorubicin/administration & dosage/adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Hodgkin Disease/*drug therapy/mortality/pathology
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Injury/chemically induced/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Peripheral Nervous System Diseases/chemically induced/epidemiology
MH  - Progression-Free Survival
MH  - United States
MH  - Vinblastine/administration & dosage/adverse effects
EDAT- 2019/01/09 06:00
MHDA- 2020/05/28 06:00
CRDT- 2019/01/09 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2018/11/12 00:00 [revised]
PHST- 2019/01/04 00:00 [accepted]
PHST- 2019/01/09 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/01/09 06:00 [entrez]
AID - 1078-0432.CCR-18-2435 [pii]
AID - 10.1158/1078-0432.CCR-18-2435 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2019 Mar 15;25(6):1718-1726. doi: 10.1158/1078-0432.CCR-18-2435. 
      Epub 2019 Jan 7.