OT1-02-09: A Phase II Randomized Trial of Lapatinib with Either Vinorelbine or Capecitabine as First- and Second-Line Therapy for HER2−Overexpressing Metastatic Breast Cancer.

Abstract

Abstract Background: Lapatinib, a dual kinase inhibitor of epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER2/ErbB2), is approved for the treatment of HER2−overexpressing (HER2+) metastatic breast cancer (MBC) in combination with capecitabine following progression after trastuzumab, anthracyclines, and taxanes. Vinorelbine is an important chemotherapy option in MBC, and multiple phase II trials in combination with trastuzumab have been conducted. Methods: This randomized, open-label, multicenter, phase II study (VITAL, LAP112620, NCT01013740) is evaluating the efficacy and safety of lapatinib with either vinorelbine or capecitabine in women with HER2+ MBC. A total of 105 stage IV breast cancer patients with disease progression who have received ≤1 chemotherapy regimen in the metastatic setting with an ECOG performance status of ≤1 are randomized 2:1 to either: lapatinib 1250 mg orally once daily (QD) continuously plus vinorelbine 20 mg/m2 intravenously on days 1 and 8 every third week; or lapatinib 1250 mg orally QD continuously plus capecitabine 2000 mg/m2/d orally in 2 doses 12 hours apart on days 1 to 14 every third week. Following progression in the randomized phase, patients will be given the option to cross over to the other arm. The primary endpoint is progression-free survival and will be analyzed with a descriptive intent since the study is not powered to detect differences between treatment arms. Secondary endpoints include overall response rate, overall survival, duration of response, time to response, and clinical benefit rate. The study is currently recruiting in 8 countries in Europe (Bulgaria, France, Germany, Greece, Italy, Poland, Serbia, Spain) and 2 in Latin America (Chile, Mexico). Funding Source: GlaxoSmithKline Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-09.