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Selected Works of Sally Lord
Article
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 (2016)
  • Chee Khoon Lee, The University of Sydney
  • Lucy Davies, The University of Sydney
  • Val Gebski, The University of Sydney
  • Sally Lord, The University of Notre Dame Australia
  • Angelo Di Leo, Istituto Toscano Tumori
  • Stephen Johnston, Royal Marsden Hospital
  • Charles Geyer Jr, Virginia Commonwealth University
  • David Cameron, The University of Edinburgh
  • Michael F Press, University of Southern California
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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 tissueHER2 (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 nonamplified
(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.
Disciplines
Publication Date
2016
DOI
10.1200/JCO.2015.62.4767
Citation Information
Lee, C., Davies, L., Gebski, V., Lord, S., Di Leo, A., Johnston, S., Geyer Jr, C., Cameron, D., Press, M., Ellis, C., Loi, S., Marschner, I., Simes, J., and 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,34(9). 936-944. DOI: 10.1200/JCO.2015.62.4767