title: Circulating heregulin level is associated with the efficacy of patritumab combined with erlotinib in patients with non-small cell lung cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  sHRG seems to be a predictive biomarker for the efficacy of patritumab plus erlotinib in NSCLC patients.
authors.affiliation: 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.
authors.forename: Kimio
authors.initials: K
authors.lastname: Yonesaka
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirotani
authors.affiliation: Asklepios Fachkliniken, 2 Robert-Koch-Allee, Gauting 82131, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.affiliation: Institute of Oncology Bucharest, 252 Fundeni Avenue, Bucharest, Romania.
authors.forename: Mircea
authors.initials: M
authors.lastname: Dediu
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Copigneaux
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayamashi, Osaka 589-8511, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000080908:Broadly Neutralizing Antibodies; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020890:Neuregulin-1 / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; C094131:NRG1 protein, human; D020890:Neuregulin-1; C585471:patritumab; D000069347:Erlotinib Hydrochloride
keywords: Erlotinib; Heregulin; Human epidermal growth factor receptor; Human epidermal growth factor receptor 3; Non-small cell lung cancer; Patritumab