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 (Study no. BIG 2-06/N06D/EGF106708).
The ALTTO trial is a phase III, randomised, multi-centre, open-label trial that employs three study designs. In Design 1, all (neo)adjuvant chemotherapy is completed prior to administration of the study treatments. In Design 2, all anthracycline-based (neo)adjuvant chemotherapy is completed prior to administration of the study treatments, while taxane is given concurrently with the study treatments. In Design 2B, a nonanthracycline regimen containing docetaxel and carboplatin is given concurrently with study treatments.
As shown in the study schema, within each design, patients are randomised to one of four treatment arms: 1) trastuzumab alone; 2) lapatinib alone; 3) trastuzumab followed by lapatinib; or 4) lapatinib in combination with trastuzumab.
75 mg/m2 IV and Carboplatin AUC 6 IV
every three weeks (6 doses)
|Trastuzumab only||Trastuzumab 2 mg/kg IV* weekly for 18 weeks, then 6 mg/kg IV every 3 weeks for 34 weeks|
|Lapatinib only||750 mg po daily for 18 weeks, then 1500 mg po daily for 34 weeks|
|Sequential||Trastuzumab 2 mg/kg IV* weekly for 18 weeks, then 6-week washout, then lapatinib 1500 mg po daily for 28 weeks|
|Combination||Lapatinib 750 mg po daily + trastuzumab 2 mg/kg IV* weekly for 18 weeks, then lapatinib 1000 mg po daily + trastuzumab 6 mg/kg IV every 3 weeks for 34 weeks|
- Histologically confirmed, nonmetastatic, primary invasive breast carcinoma
- Adequate tumour excision and axilla dissection (if positive sentinel node)
- Axillary node positive, or node negative with tumour ≥1 cm
- Known ER or ER/PgR status
- Documented overexpression and/or amplification of HER2 (ErbB2) in tumour (Central confirmation of HER2 (ErbB2) status is mandatory)
- No prior use of anti-HER2 (ErbB2) therapy
- Baseline LVEF ≥50%
- Compare disease-free survival (DFS) between each of the lapatinib-containing arms and the trastuzumab-alone arm
- Overall survival (OS)
- Time to recurrence (TTR)
- Time to distant recurrence (TTDR)
- Safety and tolerability
- Cumulative incidence of brain metastases as the first site of breast cancer recurrence
- Conduct the above analyses according to:
– cMyc gene amplification
– Expression levels of PTEN
– p95HER2 domain
The ALTTO trial also includes an extensive translational research program to identify biomarkers.
ALTTO is a global trial that will be conducted in 1300 sites in approximately 50 countries
ALTTO began enrolling patients in June 2007. The trial is now closed to enrolment (the last patient was randomised in July 2011).