Chee Khoon Lee1, Lucy Davies1, Val J Gebski1, Sarah J Lord1, Angelo Di Leo1, Stephen Johnston1, Charles Geyer1, David Cameron1, Michael F Press1, Catherine Ellis1, Sherene Loi1, Ian Marschner1, John Simes1, Paul de Souza2. 1. Chee Khoon Lee, Lucy Davies, Val J. Gebski, Sarah J. Lord, Ian Marschner, and John Simes, University of Sydney; Sarah J. Lord, University of Notre Dame; Ian Marschner, Macquarie University; Paul de Souza, University of Western Sydney, Sydney, New South Wales; Sherene Loi, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Angelo Di Leo, Hospital of Prato, Istituto Toscano Tumori, Italy; Stephen Johnston, Royal Marsden Hospital, London; David Cameron, University of Edinburgh, Edinburgh, United Kingdom; Charles Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Michael F. Press, University of Southern California, Los Angeles, CA; and Catherine Ellis, GlaxoSmithKline, Collegeville, PA. 2. Chee Khoon Lee, Lucy Davies, Val J. Gebski, Sarah J. Lord, Ian Marschner, and John Simes, University of Sydney; Sarah J. Lord, University of Notre Dame; Ian Marschner, Macquarie University; Paul de Souza, University of Western Sydney, Sydney, New South Wales; Sherene Loi, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Angelo Di Leo, Hospital of Prato, Istituto Toscano Tumori, Italy; Stephen Johnston, Royal Marsden Hospital, London; David Cameron, University of Edinburgh, Edinburgh, United Kingdom; Charles Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Michael F. Press, University of Southern California, Los Angeles, CA; and Catherine Ellis, GlaxoSmithKline, Collegeville, PA. p.desouza@uws.edu.au.
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 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; P(interaction) < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; P(interaction) = .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; P(interaction) = .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.
RCT Entities:
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 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; P(interaction) < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; P(interaction) = .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; P(interaction) = .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.
Authors: Gary A Ulaner; Jorge A Carrasquillo; Christopher C Riedl; Randy Yeh; Vaios Hatzoglou; Dara S Ross; Komal Jhaveri; Sarat Chandarlapaty; David M Hyman; Brian M Zeglis; Serge K Lyashchenko; Jason S Lewis Journal: Radiology Date: 2020-06-09 Impact factor: 11.105
Authors: Renata Duchnowska; Jeff Sperinde; Bogumiła Czartoryska-Arłukowicz; Paulina Myśliwiec; John Winslow; Barbara Radecka; Christos Petropoulos; Regina Demlova; Marlena Orlikowska; Anna Kowalczyk; Istvan Lang; Barbara Ziółkowska; Sylwia Dębska-Szmich; Monika Merdalska; Aleksandra Grela-Wojewoda; Anton Żawrocki; Wojciech Biernat; Weidong Huang; Jacek Jassem Journal: Oncotarget Date: 2017-10-24