[1090] Updated biomarker results from a phase II randomized study of lapatinib as first-line treatment for patients with ErbB2-amplified advanced or metastatic breast cancer.

Gomez HL, Chavez MA, Doval DC, Nag S, Chow LW, Chang PC, Ahmad NM, Berger M, Arbushites M, Westlund R, Stanislaus M, Zaks T, Stein S.. Instituto Especializado de Enfermedades Neoplasica, Lima, Peru; Hospital Alberto Sabogal, Lima, Peru; Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; Jehangir Hospital and Medica Centre, Pune, India; Queen Mary Hospital, Hong Kong, Hong Kong; National Cancer Centre, Singapore; Hospital University, Bharu, Kelatan, Malaysia; GlaxoSmithKline, Collegeville, PA

Background: Lapatinib is a reversible, oral small molecule inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2/neu) tyrosine kinase activity. Recent research has shown that elevated pretreatment serum ErbB2 ECD levels are associated with favorable response to trastuzumab-based therapies and that ErbB2 ECD levels decline in patients who respond to treatment. The primary objective of this study was to evaluate the response rate of two lapatinib dosing regimens as first-line treatment for patients with ErbB2-amplified advanced or metastatic breast cancer (MBC) documented by FISH. Target enrollment of 138 pts was reached in January 2006. Results reported herein pertain to IHC analysis of ErbB1, ER/PR, IGF-1R and serum ErbB2 ECD levels for these patients.
Material and methods: Eligible patients were randomized (1:1, open label) to lapatinib 1500mg as a single daily dose (QD) or lapatinib 500mg twice daily (BID). Tumor tissue was obtained from the patients most recent biopsy and was centrally analyzed for biomarker activity via IHC. Sequential evaluation of serum ErbB2 ECD levels was performed at baseline, every 4 weeks and at the end of therapy.
Results: IHC analysis of tumor tissue indicated 105 patients (76%) were ER-/PR-. Over one-third of patients (47/119, 39%) tested 3+ for IHC analysis of IGF-1R. Most subjects (95/123, 77%) were ErbB1 negative, with IHC scores of 0 (74, 60%) or 1+ (21, 17%). The median serum ErbB2 ECD level at baseline was 38.6 ng/mL, and decreased by 17% and 37% at Week 4 and Week 8, respectively.
Conclusion: Previous interim analysis results suggested an association of response to an IGF1-R score of 3+, and no association of response to ErbB1 and ER/PR status. Data on additional biomarkers and correlation of biomarker levels to clinical activity will be presented.

Thursday, December 14, 2006 5:00 PM

Poster Session I: Treatment: Chemotherapy – New Drugs and Formulations (5:00 PM-7:00 PM)