Circulating heregulin level is associated with the efficacy of patritumab combined with erlotinib in patients with non-small cell lung cancer.

Abstract

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.

• Authors: Kimio Yonesaka, Kenji Hirotani, Joachim von Pawel, Mircea Dediu, Shuquan Chen, Catherine Copigneaux, Kazuhiko Nakagawa
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 105 Pg. 1-6 (03 2017) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 28236978 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Broadly Neutralizing Antibodies
• NRG1 protein, human
• Neuregulin-1
• patritumab
• Erlotinib Hydrochloride

Topics

• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Broadly Neutralizing Antibodies
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Double-Blind Method
• Erlotinib Hydrochloride (administration & dosage, therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, metabolism)
• Male
• Neuregulin-1 (blood)
• Survival Analysis
• Treatment Outcome