PMID- 24560012
OWN - NLM
STAT- MEDLINE
DCOM- 20141201
LR  - 20220321
IS  - 1938-0690 (Electronic)
IS  - 1525-7304 (Linking)
VI  - 15
IP  - 3
DP  - 2014 May
TI  - Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor 
      necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in 
      combination with paclitaxel and carboplatin in patients with advanced 
      non-small-cell lung cancer.
PG  - 188-196.e2
LID - S1525-7304(13)00262-3 [pii]
LID - 10.1016/j.cllc.2013.12.005 [doi]
AB  - BACKGROUND: This phase II study examined the efficacy of mapatumumab in 
      combination with paclitaxel and carboplatin in patients with non-small-cell lung 
      cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB or stage IV 
      advanced primary NSCLC were randomly assigned (1:1:1) to receive up to 6 courses 
      of standard-dose paclitaxel and carboplatin or a combination of paclitaxel, 
      carboplatin, and mapatumumab (10 mg/kg or 30 mg/kg). Primary efficacy end points 
      were overall response rate and median progression-free survival (PFS). Secondary 
      efficacy end points included disease control rate, overall survival (OS), time to 
      response, and duration of response. Exploratory studies included evaluation of 
      historical biopsy materials for TRAIL-R1 expression by immunohistochemical 
      analysis and serum levels of M30, a marker of apoptosis, before and after the 
      first 2 doses of mapatumumab. Safety parameters, including adverse events (AEs), 
      laboratory tests, and immunogenicity, were assessed. RESULTS: The majority of 
      patients had stage IV disease (79%) and an Eastern Cooperative Oncology Group 
      (ECOG) performance status of 0 (58%); baseline characteristics were similar 
      across treatment arms. No improvements in response or disease control rates, PFS, 
      or OS were gained from the addition of mapatumumab. Adverse events in the 
      mapatumumab arms were generally consistent with toxicities seen in the 
      carboplatin and paclitaxel control arm. Levels of M30 were highly variable, and 
      consistent patterns were not seen across treatment arms. CONCLUSION: This study 
      showed no clinical benefit from adding mapatumumab to carboplatin and paclitaxel 
      in unselected patients with NSCLC. The combination was generally well tolerated. 
      The possibility of subgroups sensitive to mapatumumab is discussed.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - von Pawel, Joachim
AU  - von Pawel J
AD  - Department of Oncology, Asklepios-Fachkliniken Munchen-Gauting, Munich, Germany. 
      Electronic address: j.pawel@asklepios.com.
FAU - Harvey, Jimmie H
AU  - Harvey JH
AD  - Alabama Oncology, Birmingham, AL.
FAU - Spigel, David R
AU  - Spigel DR
AD  - Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN.
FAU - Dediu, Mircea
AU  - Dediu M
AD  - Department of Medical Oncology, Institute of Oncology "Prof. Dr. Alexandru 
      Trestioreanu", Bucharest, Romania.
FAU - Reck, Martin
AU  - Reck M
AD  - Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany.
FAU - Cebotaru, Cristina L
AU  - Cebotaru CL
AD  - Department of Radiotherapy I-Medical Oncology, Prof Dr Ion Chircuta Institute of 
      Oncology, Cluj, Romania.
FAU - Humphreys, Robin C
AU  - Humphreys RC
AD  - Preclinical Research, Rockville, MD.
FAU - Gribbin, Matthew J
AU  - Gribbin MJ
AD  - Department of Biostatistics, Rockville, MD.
FAU - Fox, Norma Lynn
AU  - Fox NL
AD  - Clinical Research, Human Genome Sciences, Rockville, MD.
FAU - Camidge, D Ross
AU  - Camidge DR
AD  - Division of Medical Oncology, Department of Medicine, University of Colorado, 
      Aurora, CO.
LA  - eng
SI  - ClinicalTrials.gov/NCT00583830
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131227
PL  - United States
TA  - Clin Lung Cancer
JT  - Clinical lung cancer
JID - 100893225
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
RN  - WZ1025JPGR (mapatumumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/administration & dosage
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*immunology
MH  - Survival Rate
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Carboplatin/paclitaxel combination
OT  - Death receptors
OT  - Targeted biological agent
EDAT- 2014/02/25 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/25 06:00
PHST- 2013/09/24 00:00 [received]
PHST- 2013/12/16 00:00 [revised]
PHST- 2013/12/23 00:00 [accepted]
PHST- 2014/02/25 06:00 [entrez]
PHST- 2014/02/25 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S1525-7304(13)00262-3 [pii]
AID - 10.1016/j.cllc.2013.12.005 [doi]
PST - ppublish
SO  - Clin Lung Cancer. 2014 May;15(3):188-196.e2. doi: 10.1016/j.cllc.2013.12.005. 
      Epub 2013 Dec 27.