Prognostic, predictive, and surrogate value of HER2 extracellular domain (ECD) for progression-free survival (PFS) in advanced breast cancer treated with lapatinib (lap): a meta-analysis

Chee Lee, Lucy Davies, Ian Marschner, Val Gebski, Sally Lord, Angelo Di Leo, Stephen R. D. Johnston, Charles E. Geyer, David A. Cameron, Michael F. Press, Catherine Elizabeth Ellis, Sherene Loi, John Simes, Paul De Souza

    Research output: Contribution to journalMeeting abstract


    Background: We performed a meta-analysis to determine the clinical utility of HER2 ECD in advanced breast cancer patients undergoing lap therapy. Methods: Data from Phase 3 clinical trials (EGF30001 , EGF30008 , EGF100151) of patients randomized to receive lap-containing or control treatments were analyzed. Baseline HER2 ECD (bECD) and tissue HER2 status were examined for associations with PFS. We also performed a landmark analysis to quantify the association between ECD change, as measured at 10 weeks post-randomization, with PFS, and assessed the extent ECD change predicted lap benefit. Results: Levels of bECD were higher in HER2+ (n=378) than HER2- (n=1060) patients (61.59 vs 14.25ng/ml, p<0.0001). The effectiveness of lap was significantly associated with bECD (joint treatment-biomarker interactions P=0.001[bECD], P=0.02[HER2 tissue status]). At 10 weeks post-randomization, there was a mean 4.23ng/ml reduction in ECD with no significant difference between treatment arms (lap: 4.33ng/ml, control: 4.12ng/ml; P=0.92). In the control arms, change in ECD was prognostic for PFS (P<0.0001). The median PFS from landmark (mPFS) were 9.8 and 2.9 months for those with low ECD (≤15ng/ml) and high ECD (>15ng/ml), respectively. mPFS were 3.3 and 5.7 months for patients with ECD increase to >15ng/ml and ECD decrease to ≤15ng/ml, respectively. Similar finding was observed in the experimental arm (P<0.0001). In both treatment arms, there was 4% increase in risk of disease progression for every 10 unit ECD increment after adjustment of bECD and other factors (P<0.0001). Lap improved PFS over control (HR 0.83, P=0.002). Adjustment for ECD change yielded a similar result (HR 0.80, P<0.001), indicating that change in ECD did not explain the treatment effect of lap. Conclusions: Baseline HER2 ECD was predictive of lap benefit. ECD increase during lap and non-lap therapies was associated with a shorter PFS. Change in ECD had additional prognostic information in addition to baseline ECD, but was not a valid surrogate marker for lapatinib benefit as the treatment effect of lap was largely independent of ECD change.
    Original languageEnglish
    Pages (from-to)630-630
    Number of pages1
    JournalJournal of Clinical Oncology
    Issue number15, suppl.
    Publication statusPublished - 20 May 2014
    Event50th Annual Meeting of the American-Society-of-Clinical-Oncology - Chicago, United States
    Duration: 30 May 20143 Jun 2014


    Dive into the research topics of 'Prognostic, predictive, and surrogate value of HER2 extracellular domain (ECD) for progression-free survival (PFS) in advanced breast cancer treated with lapatinib (lap): a meta-analysis'. Together they form a unique fingerprint.

    Cite this