An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study)

R. C. Coombes, T. Tat, M. L. Miller, J. A. Reise, J. L. Mansi, D. J. Hadjiminas, S. Shousha, S. E. Elsheikh, E. W-F. Lam, Y. Horimoto, M. El-Bahrawy, E. O. Aboagye, K. B. Contractor, J. A. Shaw, R. A. Walker, M. H. Marconell, C. Palmieri, J. Stebbing*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    Background
    This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naive patients with HER-2-negative primary breast cancer.

    Patients and methods
    Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3.

    Results
    Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 >= 50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders.

    Conclusion
    Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.

    Original languageEnglish
    Pages (from-to)924-930
    Number of pages7
    JournalAnnals of Oncology
    Volume24
    Issue number4
    DOIs
    Publication statusPublished - Apr 2013

    Keywords

    • biomarker
    • breast
    • HER-3
    • Ki67
    • lapatinib
    • pre-surgical
    • ESTROGEN-RECEPTOR
    • PHASE-II
    • PROGESTERONE-RECEPTOR
    • RANDOMIZED-TRIAL
    • GEFITINIB IRESSA
    • EXPRESSION
    • RECOMMENDATIONS
    • PROLIFERATION
    • TRASTUZUMAB
    • MONOTHERAPY

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