Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy.

BACKGROUND: Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/ or PFS in patients with MBC receiving first-line lapatinib monotherapy. METHODS: The EGF20009 study investigated lapatinib monotherapy in 138 HER2-positive patients with MBC previously untreated for their metastatic disease. Serum was collected and assessed at baseline and every 4 weeks for 16 weeks after treatment initiation. Disease assessment was performed at weeks 8 and 12 and every 12 weeks thereafter. A >= 20% decrease or increase in serum HER2 was defined as a significant change. RESULTS: Seventy-nine percent of patients had elevated baseline serum HER2. Baseline serum HER2 was associated with ORR (P = .043) but not PFS. Patients with a >= 20% decrease from baseline of serum HER2 at weeks 4, 8, 12, and 16 had a significantly increased ORR and prolonged PFS. Conversely, those with a >= 20% increase from baseline had a significantly lower ORR and shorter PFS. CONCLUSION: Significant decreases in serum HER2 levels during the first 16 weeks of lapatinib monotherapy were associated with better clinical outcome (longer PFS and increased ORR) in HER2-positive MBC patients. Cancer 2011; 117: 5013-20. (C) 2011 American Cancer Society.