Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer

Chee Khoon Lee, Lucy Davies, Val J. Gebski, Sarah J. Lord, Angelo Di Leo, Stephen Johnston, Charles Geyer, David Cameron, Michael F. Press, Catherine Ellis, Sherene Loi, Ian Marschner, John Simes, Paul De Souza

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. Patients and Methods: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Results: Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and non-amplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; Pinteraction <.001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; Pinteraction = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; Pinteraction = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P <.001; and OS, 1.018; P <.001). Conclusion: Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.

Original languageEnglish (US)
Pages (from-to)936-944
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number9
DOIs
StatePublished - Mar 20 2016

Fingerprint

Epidermal Growth Factor
Biomarkers
Disease-Free Survival
Breast Neoplasms
Serum
Survival
Therapeutics
Safety Management
lapatinib
Regression Analysis
Research
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer. / Lee, Chee Khoon; Davies, Lucy; Gebski, Val J.; Lord, Sarah J.; Di Leo, Angelo; Johnston, Stephen; Geyer, Charles; Cameron, David; Press, Michael F.; Ellis, Catherine; Loi, Sherene; Marschner, Ian; Simes, John; De Souza, Paul.

In: Journal of Clinical Oncology, Vol. 34, No. 9, 20.03.2016, p. 936-944.

Research output: Contribution to journalArticle

Lee, CK, Davies, L, Gebski, VJ, Lord, SJ, Di Leo, A, Johnston, S, Geyer, C, Cameron, D, Press, MF, Ellis, C, Loi, S, Marschner, I, Simes, J & De Souza, P 2016, 'Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer', Journal of Clinical Oncology, vol. 34, no. 9, pp. 936-944. https://doi.org/10.1200/JCO.2015.62.4767
Lee, Chee Khoon ; Davies, Lucy ; Gebski, Val J. ; Lord, Sarah J. ; Di Leo, Angelo ; Johnston, Stephen ; Geyer, Charles ; Cameron, David ; Press, Michael F. ; Ellis, Catherine ; Loi, Sherene ; Marschner, Ian ; Simes, John ; De Souza, Paul. / Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 9. pp. 936-944.
@article{e9b3b0e582684607b446dc89cf7c0ce5,
title = "Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer",
abstract = "Purpose: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. Patients and Methods: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84{\%}) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Results: Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and non-amplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; Pinteraction <.001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; Pinteraction = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; Pinteraction = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P <.001; and OS, 1.018; P <.001). Conclusion: Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.",
author = "Lee, {Chee Khoon} and Lucy Davies and Gebski, {Val J.} and Lord, {Sarah J.} and {Di Leo}, Angelo and Stephen Johnston and Charles Geyer and David Cameron and Press, {Michael F.} and Catherine Ellis and Sherene Loi and Ian Marschner and John Simes and {De Souza}, Paul",
year = "2016",
month = "3",
day = "20",
doi = "10.1200/JCO.2015.62.4767",
language = "English (US)",
volume = "34",
pages = "936--944",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

TY - JOUR

T1 - Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer

AU - Lee, Chee Khoon

AU - Davies, Lucy

AU - Gebski, Val J.

AU - Lord, Sarah J.

AU - Di Leo, Angelo

AU - Johnston, Stephen

AU - Geyer, Charles

AU - Cameron, David

AU - Press, Michael F.

AU - Ellis, Catherine

AU - Loi, Sherene

AU - Marschner, Ian

AU - Simes, John

AU - De Souza, Paul

PY - 2016/3/20

Y1 - 2016/3/20

N2 - Purpose: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. Patients and Methods: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Results: Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and non-amplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; Pinteraction <.001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; Pinteraction = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; Pinteraction = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P <.001; and OS, 1.018; P <.001). Conclusion: Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.

AB - Purpose: We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. Patients and Methods: We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Results: Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and non-amplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; Pinteraction <.001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; Pinteraction = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; Pinteraction = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P <.001; and OS, 1.018; P <.001). Conclusion: Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.

UR - http://www.scopus.com/inward/record.url?scp=84962052834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962052834&partnerID=8YFLogxK

U2 - 10.1200/JCO.2015.62.4767

DO - 10.1200/JCO.2015.62.4767

M3 - Article

C2 - 26811533

AN - SCOPUS:84962052834

VL - 34

SP - 936

EP - 944

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -