• SAN ANTONIO—The investigational agent lapatinib (Tykerb) when added to paclitaxel(Drug information on paclitaxel) has significant clinical activity as neoadjuvant treatment of HER2-positive inflammatory breast cancer (IBC), Massimo Cristofanilli, MD, of M.D. Anderson Cancer Center, reported at the 29th Annual San Antonio Breast Cancer Symposium (abstract 1).
Inflammatory breast cancer, the most lethal form of breast cancer, tends to express ErbB1 (epidermal growth factor receptor [EGFR]) and overexpress ErbB2 (HER2/neu). The small molecule tyrosine kinase inhibitor lapatinib targets both ErbB1 and B2 tyrosine kinases.
The EGF102580 international phase II trial was initiated "because lapatinib is one of the few drugs that had shown any activity in phase I studies in patients with recurrent IBC," Dr. Cristofanilli said. "It appeared that this agent could be the first to offer hope for women newly diagnosed with the disease."
Dr. Cristofanilli reported on 35 patients with newly diagnosed inflammatory breast cancer who completed the trial and underwent surgery. All patients had advanced disease, and most had hormone-receptor-negative tumors.
Cohort A overexpressed HER2 while cohort B included patients who were ErbB1 positive and HER2 negative. All patients received lapatinib 1,500 mg orally once daily as monotherapy on days 1 to 14, followed by an additional 12 weeks in combination with weekly paclitaxel 80 mg/m2. After 14 weeks of treatment, patients underwent surgery followed by adjuvant chemotherapy, radiotherapy, or hormonal therapy at the treating oncologist's discretion.
In the 30 HER2-positive patients, lapatinib as monotherapy during the first 14 days produced clinical responses in 30% of patients. Functional imaging done for some of the patients after 2 weeks demonstrated evidence of a metabolic response to lapatinib, Dr. Cristofanilli said.
The combination of lapatinib plus paclitaxel produced a response rate of 77% (10% complete responses and 67% partial responses), and stable disease in 10% of patients. Notably, 17% of patients who underwent surgery had a pathological complete response (pCR), ie, no evidence of residual invasive tumor, even in the axillary lymph nodes.
