OT1-02-02: HALT MBC: HER2 Suppression with the Addition of Lapatinib to Trastuzumab in HER2−Positive Metastatic Breast Cancer (LPT112515).

Abstract

Abstract Background Lapatinib in combination with trastuzumab enhanced anti-tumor activity in HER2−positive breast cancer (BC) preclinical models. In patients (pts) with trastuzumab-treated, HER2−positive metastatic (M) BC, treatment with the combination was associated with longer progression-free (PFS) and overall survival (OS) compared with lapatinib alone. In pts with stage II/III BC, preoperative treatment with the combination plus paclitaxel resulted in significantly higher pathological complete response rates compared with paclitaxel combined with either agent alone. This evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2−positive BC. This present study is designed to evaluate whether the addition of lapatinib improves PFS among women with HER2−positive MBC receiving trastuzumab as maintenance therapy. Trial Design In this open-label, Phase III study, pts are stratified by line of treatment (first/second) and hormone receptor status (positive/negative) then randomized 1:1 to receive maintenance treatment with either lapatinib (1000mg once daily, continuously) in combination with trastuzumab (6mg/kg once every 3 weeks [Q3W]) or trastuzumab (6mg/kg Q3W) alone. Pts will receive study treatment until disease progression, death, discontinuation due to adverse events or other reasons. Eligibility Criteria Pts with HER2−positive MBC who have completed 12–24 weeks of first- or second-line treatment with trastuzumab plus chemotherapy and have objective response or stable disease. Pts with stable brain metastasis are eligible if entering the study on second-line treatment. Specific Aims The primary objective is to compare PFS of lapatinib in combination with trastuzumab to trastuzumab as continued HER2 suppression therapy. Secondary objectives are to evaluate OS, clinical benefit rate, safety and tolerability. Statistical Methods Efficacy endpoints will be analyzed in the intent to treat population. A total of 193 PFS events from 280 randomized pts will be required to detect a 50% increase in median PFS in pts who receive lapatinib plus trastuzumab compared with trastuzumab (median PFS time is 27 versus 18 weeks, respectively); hazard ratio of 0.67 with an 80% power and a 1-sided type I error of 0.025. Present and Target Accrual Sixteen of the target 280 pts have been randomized. The trial is currently open for accrual in the United States and Canada. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-02.