PMID- 28236978
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20220409
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 105
DP  - 2017 Mar
TI  - Circulating heregulin level is associated with the efficacy of patritumab 
      combined with erlotinib in patients with non-small cell lung cancer.
PG  - 1-6
LID - S0169-5002(16)30585-2 [pii]
LID - 10.1016/j.lungcan.2016.12.018 [doi]
AB  - OBJECTIVES: Patritumab is a fully human anti-human epidermal growth factor 
      receptor 3 (HER3) antibody that blocks activation by its ligand, heregulin (HRG). 
      Preclinical studies have demonstrated the efficacy of patritumab in aberrantly 
      high HRG-expressing non-small cell lung cancer (NSCLC). In the phase II 
      randomized, placebo-controlled double-blind study HERALD (n=212 patients with 
      NSCLC), patritumab plus erlotinib did not improve progression-free survival (PFS) 
      compared with placebo plus erlotinib. The current study examined whether soluble 
      HRG (sHRG) level in serum correlated with the efficacy of patritumab plus 
      erlotinib. MATERIALS AND METHODS: Serum was obtained from participants prior to 
      treatment (n=202). sHRG level was measured using a validated quantitative immune 
      assay, and correlations with survival were blindly assessed. RESULTS: sHRG level 
      was various (-1346-11,772pg/mL). Participants were divided into the sHRG-high or 
      -low subgroups at the concentration defining near the third quartile, 980pg/mL. 
      Patritumab plus erlotinib significantly improved PFS relative to placebo in the 
      sHRG-high subgroup (n=46, hazard ratio 0.42 [0.19-0.96], p=0.0327). In contrast, 
      the HRG-low subgroup (n=148) had no improvement in PFS with patritumab. 
      CONCLUSION: sHRG seems to be a predictive biomarker for the efficacy of 
      patritumab plus erlotinib in NSCLC patients.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Yonesaka, Kimio
AU  - Yonesaka K
AD  - Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 
      Ohno-higashi, Osaka-Sayamashi, Osaka 589-8511, Japan. Electronic address: 
      yonesaka@sakai.med.kindai.ac.jp.
FAU - Hirotani, Kenji
AU  - Hirotani K
AD  - Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
FAU - von Pawel, Joachim
AU  - von Pawel J
AD  - Asklepios Fachkliniken, 2 Robert-Koch-Allee, Gauting 82131, Germany.
FAU - Dediu, Mircea
AU  - Dediu M
AD  - Institute of Oncology Bucharest, 252 Fundeni Avenue, Bucharest, Romania.
FAU - Chen, Shuquan
AU  - Chen S
AD  - Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA.
FAU - Copigneaux, Catherine
AU  - Copigneaux C
AD  - Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA.
FAU - Nakagawa, Kazuhiko
AU  - Nakagawa K
AD  - Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 
      Ohno-higashi, Osaka-Sayamashi, Osaka 589-8511, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170109
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Broadly Neutralizing Antibodies)
RN  - 0 (NRG1 protein, human)
RN  - 0 (Neuregulin-1)
RN  - 86780VJI1Q (patritumab)
RN  - DA87705X9K (Erlotinib Hydrochloride)
SB  - IM
MH  - Antibodies, Monoclonal/*administration & dosage/therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibodies, Neutralizing/*administration & dosage/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & 
      dosage/therapeutic use
MH  - Broadly Neutralizing Antibodies
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Erlotinib Hydrochloride/*administration & dosage/therapeutic use
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Male
MH  - Neuregulin-1/*blood
MH  - Survival Analysis
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Erlotinib
OT  - Heregulin
OT  - Human epidermal growth factor receptor
OT  - Human epidermal growth factor receptor 3
OT  - Non-small cell lung cancer
OT  - Patritumab
EDAT- 2017/02/27 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/02/27 06:00
PHST- 2016/08/09 00:00 [received]
PHST- 2016/12/16 00:00 [revised]
PHST- 2016/12/22 00:00 [accepted]
PHST- 2017/02/27 06:00 [entrez]
PHST- 2017/02/27 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
AID - S0169-5002(16)30585-2 [pii]
AID - 10.1016/j.lungcan.2016.12.018 [doi]
PST - ppublish
SO  - Lung Cancer. 2017 Mar;105:1-6. doi: 10.1016/j.lungcan.2016.12.018. Epub 2017 Jan 
      9.