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

doi:10.1093/annonc/mds594

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 journal › Article › peer-review

14 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 language	English
Pages (from-to)	924-930
Number of pages	7
Journal	Annals of Oncology
Volume	24
Issue number	4
DOIs	https://doi.org/10.1093/annonc/mds594
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Coombes, R. C., Tat, T., Miller, M. L., Reise, J. A., Mansi, J. L., Hadjiminas, D. J., Shousha, S., Elsheikh, S. E., Lam, E. W.-F., Horimoto, Y., El-Bahrawy, M., Aboagye, E. O., Contractor, K. B., Shaw, J. A., Walker, R. A., Marconell, M. H., Palmieri, C., & Stebbing, J. (2013). An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study). Annals of Oncology, 24(4), 924-930. https://doi.org/10.1093/annonc/mds594

@article{03862a87997a4c11bd986e7016f753f3,

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

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.",

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

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

year = "2013",

month = apr,

doi = "10.1093/annonc/mds594",

language = "English",

volume = "24",

pages = "924--930",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier",

number = "4",

}

Coombes, RC, Tat, T, Miller, ML, Reise, JA, Mansi, JL, Hadjiminas, DJ, Shousha, S, Elsheikh, SE, Lam, EW-F, Horimoto, Y, El-Bahrawy, M, Aboagye, EO, Contractor, KB, Shaw, JA, Walker, RA, Marconell, MH, Palmieri, C & Stebbing, J 2013, 'An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study)', Annals of Oncology, vol. 24, no. 4, pp. 924-930. https://doi.org/10.1093/annonc/mds594

TY - JOUR

T1 - An open-label study of lapatinib in women with HER-2-negative early breast cancer

T2 - the lapatinib pre-surgical study (LPS study)

AU - Coombes, R. C.

AU - Tat, T.

AU - Miller, M. L.

AU - Reise, J. A.

AU - Mansi, J. L.

AU - Hadjiminas, D. J.

AU - Shousha, S.

AU - Elsheikh, S. E.

AU - Lam, E. W-F.

AU - Horimoto, Y.

AU - El-Bahrawy, M.

AU - Aboagye, E. O.

AU - Contractor, K. B.

AU - Shaw, J. A.

AU - Walker, R. A.

AU - Marconell, M. H.

AU - Palmieri, C.

AU - Stebbing, J.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

KW - biomarker

KW - breast

KW - HER-3

KW - Ki67

KW - lapatinib

KW - pre-surgical

KW - ESTROGEN-RECEPTOR

KW - PHASE-II

KW - PROGESTERONE-RECEPTOR

KW - RANDOMIZED-TRIAL

KW - GEFITINIB IRESSA

KW - EXPRESSION

KW - RECOMMENDATIONS

KW - PROLIFERATION

KW - TRASTUZUMAB

KW - MONOTHERAPY

U2 - 10.1093/annonc/mds594

DO - 10.1093/annonc/mds594

M3 - Article

SN - 0923-7534

VL - 24

SP - 924

EP - 930

JO - Annals of Oncology

JF - Annals of Oncology

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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