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

• Published in: Annals of oncology Vol. 24; no. 4; pp. 924 - 930
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2013; Oxford University Press
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; biomarker; Biopsy; breast; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Proliferation - drug effects; ErbB Receptors - metabolism; Female; Forkhead Box Protein M1; Forkhead Box Protein O3; Forkhead Transcription Factors - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Gynecology. Andrology. Obstetrics; HER-3; Humans; Ki-67 Antigen - metabolism; Ki67; Lapatinib; Mammary gland diseases; Medical sciences; Middle Aged; Oncogene Protein v-akt - metabolism; Pharmacology. Drug treatments; pre-surgical; Quinazolines - administration & dosage; Receptor, ErbB-2 - genetics; Receptor, ErbB-3 - metabolism; Receptors, Estrogen - metabolism; Tumors; pre-surgical; lapatinib; biomarker; HER-3; Ki67; breast; Antineoplastic agent; Breast disease; erbB2 Gene; Biological marker; Surgery; Lipopolysaccharide; Adult; Female; Mammary gland; Lapatinib; Woman; Protein-tyrosine kinase; Protooncogene; Human; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Breast cancer; Malignant tumor; Human Epidermal growth factor Receptor 2; Human Epidermal growth factor Receptor 3; Mammary gland diseases; Treatment; C-Onc gene; Ki67 antigen; Breast; Early; Cancer
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mds594

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