Center for Oncology Research & Treatment–Dallas, TX

CORT has opened the NCCTG N063D (BIG 2-06) study for adjuvant therapy of her-2 positive breast cancer.  This study is a worldwide study funded by the National Cancer Institute Cooperative Group (NCCTG).  It is known as the ALLTO study. 

Her-2 (ErbB-2) is a protein which can drive the growth of breast cancer.   It is overexpressed on the cancer cell surface in as many as 25% of breast cancers.  That expression is a result of amplification of the Her-2 gene in those cases.  Standard adjuvant therapy for her-2 positive breast cancer includes treatment with chemotherapy and trastuzumab (Herceptin).  Trastuzumab is a monoclonal antibody that blocks her-2 protein on the cancer cell surface.  Several studies (NSABP B-31, NCCTG N9831, FinHer, BCIRG 006) established the role of adding trastuzumab to adjuvant chemotherapy, with significant (50%) relative risk reduction in the recurrence risk of disease recurrence.  At the present time, standard therapy may consist of a sequence of doxorubicin (Adriamycin) and cyclophosphamide (AC), followed by taxane therapy, with trastuzumab given during the taxane portion of that treatment.  In addition, trastuzumab therapy is given as maintenance for a duration of one year. 

The ALLTO study compares the effectiveness of another anti-her-2 drug, either alone or in combination with trastuzumab.  That drug is lapatinib (Tykerb).  Lapatinib is an oral drug.  Lapatinib has a different mode of blocking the her-2 protein.  Lapatinib binds the intracellular (inside the cell) portion of the her-2 molecule, stopping the action her-2 from activating other signaling proteins in the cell.  Lapatinib is approved in combination with chemotherapy (capecitabine=Xeloda) for treating metastatic breast cancer that has progresed after at least one trastuzumab-chemotherapy combination therapy.  The ALLTO study is moving lapatinib therapy into the adjuvant treatment setting.

There are two treatment designs in the ALLTO study.  The physician will select the treatment design that he feels most appropriate for the patient’s care.  Patients in group 1 (design 1) will complete all of their chemotherapy before starting anti-her-2 therapy.  Patients in group 2 (design 2) will complete standard AC therapy, and then have standard weekly paclitaxel (Taxol) therapy.  In group 2, the anti-her-2 therapy will begin at the same time as the initiation of paclitaxel therapy.  In both groups, the patients will be randomized between four anti-her-2 treatments: 1) lapatinib daily for one year, 2) trastuzumab for one year, 3) trastuzumab for 12 weeks, followed by 6 weeks of no therapy, then lapatinib for 34 weeks, and 4) lapatinib and trastuzumab for 52 weeks.  The schema for design 2 is depicted below.

altto-study-schema-design-2

Efficacy, safety, and tolerability will be evaluated.

For more information about the ALTTO study, visit the CORT website at www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588 (Dallas), or 972-981-4012 (Plano).

Tags: adjuvant therapy, adjuvant treatment, ALLTO study, BIG 2-06, Breast Cancer, her-2, her-2/neu, her2, Herceptin, lapatinib, N063D, NCCTG, trastuzumab, Tykerb

This entry was posted on November 10, 2008 at 9:18 pm and is filed under Breast Cancer. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.