HER2, p95HER2, and HER3 expression and treatment outcome of lapatinib plus capecitabine in HER2-positive, trastuzumab-refractory metastatic breast cancer.

1088 Background: Lapatinib (L) is a dual tyrosine kinase inhibitor of EGFR and HER2. Lapatinib plus capecitabine (C) is an effective treatment option in trastuzumab (T)-refractory HER2-positive (+) metastatic breast cancer (MBC). However, predictive biomarkers for this treatment are not known. This study sought to investigate correlation of quantitative measurements of HER family proteins and treatment outcome in HER2+, T-refractory MBC patients (pts) treated with L plus C. Methods: Total HER2 (H2T), HER2 homodimer (H2D), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin-fixed paraffin-embedded samples using the VeraTag assay (Monogram Biosciences, CA). HER2+ (either IHC 3+ or FISH+) MBC pts who had progressed after prior therapy including anthracycline, taxane, and T were included. Patients received L 1,250mg/day D1-21 and C 2,000mg/m2/day D1-14 every 21 days according to Lapatinib Expanded Access Program. The association between protein expression levels and clinical outcomes was analyzed. Results: 59 pts with tissues available for testing were included. H2T, H2D, p95, and H3T were assessable in 52, 51, 49, and 47 pts, respectively. Best overall response according to RECIST in the study population was PR in 11 (21.2%), SD in 30 (57.7%) and PD in 11 (21.2%). Median time-to-progression (TTP) was 4.4 months (mos) and overall survival 14 mos. H2T (median 63.9 in PR, 45.5 in SD, and 17.3 in PD; p > 0.026) and H2D (median 36.7 in PR, 32.3 in SD, and 27.9 in PD; p > 0.014) levels were significantly higher in responders. Longer TTP was associated with high H2T [high (>14.95), 5.0 mos vs. low (≤14.95), 1.4 mos; p > 0.026]. Pts with both high H2T and high H3T showed disease control rate (PR+SD) at 3 mos of 84.2% (16/19) vs. 46.4% (13/28) in the others (p > 0.009) and median TTP of 5.2 mos vs. 3.0 mos in the others (p > 0.010). No significant association between p95 and response or survival was observed. Conclusions: These data suggest a correlation between high H2T and H3T levels and treatment outcome of L plus C in the study population, while clinical outcomes were similar regardless of p95 expression level. These results require confirmation in further studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Monogram Biosciences