A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer
A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer
This was a four-arm (parallel group) randomized, open-label, multicenter Phase 3 study to investigate the use of a combination of Lapatinib and Trastuzumab, a sequence of Trastuzumab followed by Lapatinib, and Lapatinib alone, compared to Trastuzumab alone in the adjuvant treatment of Human Epidermal Growth Factor Receptor 2 (HER2) positive early breast cancer.
Treatment allocation was stratified by blocked randomization, with three stratification factors:
The primary objective of this study was to compare disease-free survival (DFS) in subjects with HER2 overexpressing and/or amplified breast cancer randomized to trastuzumab for one year versus lapatinib for one year versus trastuzumab (12 or 18 weeks, according to assigned design) followed by a six week treatment-free interval followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year (52 weeks).
Secondary objectives included treatment comparisons with respect to overall survival, time to recurrence, time to distant recurrence, safety and tolerability, and incidence of brain metastasis.
Based on the recommendation of the Independent Data Monitoring Committee (IDMC) at the first interim analysis (18-Aug-2011), the Lapatinib alone arm was discontinued prior to primary analysis due to futility. The IDMC also stated that the other three arms (trastuzumab alone, sequential trastuzumab/lapatinib arm and the combination arm) could continued as planned with no changes.
Key Inclusion Criteria:
Key Exclusion Criteria:
History of any prior (ipsi- and/or contralateral) invasive breast carcinoma, past (less than 10 years) or current history of malignant neoplasms, any clinically staged T4 tumor, or bilateral tumors.
Concurrent anti-cancer treatment, except hormonal therapy or radiotherapy for the present breast cancer;
Patients with positive or suspicious internal mammary nodes identified by sentinel node technique, which had not been irradiated or would not be irradiated, or patients with supraclavicular lymph node involvement.
Any prior anti-HER therapy, which includes agents that target other members of the HER family of receptors, e.g. gefitinib (Iressa)
(Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support;
Serious cardiac illness or medical conditions.
Any of the following abnormal laboratory tests immediately prior to randomization:
Women of childbearing potential and male patients with partners of childbearing potential, who are unable or unwilling to use adequate contraceptive measures during study treatment, and pregnant or lactating women.
Concomitant use of CYP3A4 inhibitors or inducers.
East Bentleigh, 3165, Australia
Porte Alegre, 90430-001, Brazil
Arhus C, 8000, Denmark
Hilleroed, 3400, Denmark
Koebenhavn Oe, 2100, Denmark
Perin Sur Mer, 22190, France
Hamm-Heessen, 59073, Germany
Zrifin, 70300, Israel
Ehime, 791-0280, Japan
Sittard-Geleen, 6162 BG, Netherlands
Vizcaya, 48903, Spain
Tainan County, 736, Taiwan
Gwynedd, LL57 2PW, United Kingdom
Prittlewell Chase, SS0 0RY, United Kingdom