A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses

• DOI: 10.1007/s10549-007-9885-0
• Publication Date: 2008-01-10T07:54:07Z
• Authors: David Cameron; Michelle Casey; Michael Press; Deborah Lindquist; Tadeusz Pienkowski; C. Gilles Romieu; Stephen Chan; Agnieszka Jagiell...; Bella Kaufman; John Crown; Arlene Chan; Mario Campone; Patrice Viens; Neville Davidson; Vera Gorbounova; Johannes Isaac Raats; Dimosthenis Skarlos; Beth Newstat; Debasish Roychowd...; Paolo Paoletti; Cristina Oliva; Stephen Rubin; Steven Stein; Charles E. Geyer
• Keywords: Adult; Aged, 80 and over; Antibodies, Monoclonal; Breast Neoplasms; Lapatinib; Middle Aged; Protein-Tyrosine Kinases; Trastuzumab; Antibodies, Monoclonal, Humanized; Deoxycytidine; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease Progression; Quinazolines; Humans; Female; Fluorouracil; Neoplasm Metastasis; Capecitabine; Aged

Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported.Women with HER2-positive, locally advanced or metastatic breast cancer previously treated with anthracycline-, taxane-, and trastuzumab-containing regimens were randomized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m(2) days 1-14 of a 21-day cycle or capecitabine 2,500 mg/m(2) on the same schedule. The primary endpoint was time to progression (TTP) as determined by an independent review panel. Relationship between progression-free survival (PFS) and tumor HER2 expression and serum levels of HER2 extracellular domain (ECD) were assessed.399 women were randomized. The addition of lapatinib prolonged TTP with a hazard ratio (HR) of 0.57 (95% CI, 0.43-0.77; P < 0.001) and provided a trend toward improved overall survival (HR: 0.78, 95% CI: 0.55-1.12, P = 0.177), and fewer cases with CNS involvement at first progression (4 vs. 13, P = 0.045). Baseline serum HER2 ECD did not predict for benefit from lapatinib.The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.