Posts Tagged ‘Herceptin’

New Treatment for Her-2+ Metastatic Breast Cancer Opens at CORT

September 4, 2009

CORT has opened the Wyeth 3144A2 3005 WW Study testing the oral her-2 inhibitor, neratinib, in combination with paclitaxel (Taxol), versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. 

Neratinib is an oral anti-her-1/her-2 drug with demonstrated efficacy in metastatic her-2 positive breast cancer.  The safety studies have demonstrated acceptable and manageable toxicity of neratinib, including rash and occasional loose stools or diarrhea being most common.  As with other her-2 inhibiting drugs, neratinib may lower the cardiac ejection fraction, so serial monitoring of cardiac function is routine.  The Phase III study will compare the efficacy and tolerability of paclitaxel with either oral neratinib or trastuzumab (a monoclonal antibody against her-2 protein, given IV).

The potential advantages of neratinib include improved convenience (and possibly improved safety).  The drug is given orally.  

For more information about this study, visit our website at, or contact a Research Coordinator at 972-566-5588.  

Patients with her-2+ breast cancer may also be eligible for other studies and treatment at CORT, including non-study therapy.  The principle investigator at CORT is Dr. Barry Mirtsching.  He has personally conducted over 200 trials in cancer therapy over 16 years, many in breast cancer management.  Experience in both trial and non-trial breast cancer management benefits patients by producing better treatment outcomes.  Care at CORT is individual and personal, with adequate time for problem-solving and direct contact with the physician.

TDM1 (Trastuzumab-DM1) Immunoconjugate Drug Therapy Study Open at CORT

December 10, 2008

A phase III study of Trastuzumab-DM1 for treatment of relapsed her-2 positive metastatic breast cancer is open at CORT. 

Trastuzumab (Herceptin)  is a monoclonal antibody against the her-2 protein, which is overexpressed or amplified in an aggressive subset of breast cancers.  Trastuzumab and chemotherapy combination therapy has substantially improved response, progression-free survival, and overall survival of metastatic her-2 positive breast cancer patients.  Trastuzumab is approved for treatment of metastatic breast cancer.  Trastuzumab may be associated with uncommon infusion reactions and myocardial dysfunction, which may produce clinical congestive heart failure in about 1% of patients, which may be reversible in some cases with discontinuation of therapy.  When her-2 positive metastatic breast cancer progresses on a first-line trastuzumab + chemotherapy regimen, continuing trastuzumab (or another anti-her-2 drug) in the second-line treatment setting (with a different chemotherapy drug) is beneficial with regard to response and stopping disease progression (compared to therapy with chemotherapy alone). 

Lapatinib (Tykerb) is an oral drug that inhibits the intracellular, activating portion of the her-2 molecule.  It has been approved (in combination with capecitabine (Xeloda)) for treatment of metastatic her-2 positive breast cancer that has progressed after trastuzumab-based initial therapy. 

Trastuzumab-DM1 (TDM1) is a drug that combines trastuzumab with a linked chemotherapy agent, maytansine (DM1).   This linkage of an antibody and a drug is termed an immunoconjugate.  The potential advantage of immunoconjugate therapy is that the antibody targets DM1 specifically into tumorous tissue, which may reduce the toxicity of treatment.   In addition, the antibody trastuzumab has it’s own anti-cancer activity.  TDM1 has been tested in open-label phase I and II studies, with mild toxicities and effectiveness, even in heavily pre-treated her-2 positive metastatic breast cancer.  Adverse events that have been noted include elevated liver function tests, fatigue, anemia, and thrombocytopenia. 

The Phase III study at CORT is part of a large multicenter national study.  The study will test the activity of trastuzumab-DM1 versus standard therapy (lapatinib-capecitabine) for second-line therapy of patients with metastatic her-2 positive breast cancer.

For more information about this study, consultation, or referral, contact a CORT Research Coordinator at 972-566-5588, or visit our website at

ALLTO Study Evaluates the Role of Lapatinib (Tykerb) in Adjuvant Therapy of Her-2 Positive Breast Cancer

November 10, 2008

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.


Efficacy, safety, and tolerability will be evaluated.

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

Lapatinib (Tykerb) for Treatment of Metastatic Breast Cancer

September 27, 2007

According to results recently presented at the 2007 annual meeting of the American Society of Clinical Oncology, the targeted agent Tykerb® (lapatinib) may be effective in shrinking cancer that has spread to the brain among some patients with breast cancer.Tykerb is a targeted therapy that has produced promising results in women with metastatic or refractory breast cancer. Targeted therapies are anticancer drugs that are designed to treat cancer cells while reducing damage to normal, healthy cells. Tykerb targets two proteins that often function abnormally in breast cancer cells—HER2 and EGFR. When these proteins are increased in cancer cells (a condition referred to as HER2-positive and/or EGFR-positive cancers), the proteins tend to function abnormally, resulting in uncontrolled, faster growth of cancerous cells. Tykerb decreases or prevents the growth of these cancerous cells.Researchers recently reported results from a clinical study that suggested Tykerb may have anticancer activity among patients with brain metastasis from advanced HER2-positive breast cancer. This study included 241 patients whose brain metastasis continued to progress following therapy with Herceptin® (trastuzumab) and radiation therapy.Nearly half of the patients (46%) experienced at least a 20% reduction in the size of their brain metastasis.An additional 42% of patients achieved stabilization of their disease for at least eight weeks.Overall, 22% of patients had no signs of disease progression within the first six months of treatment with Tykerb.

The most common severe side effects were diarrhea, skin rash, nausea, vomiting, and fatigue.

The researchers concluded that among patients with advanced breast cancer: “Tykerb has promise in the treatment of brain metastases.” Further study of Tykerb in advanced breast cancer is ongoing at CORT. We are conducting a trial of Tykerb with either capecitabine (Xeloda) or topotecan (Hycamptin) chemotherapy for treatment of patients whose brain metastases continue to progress following treatment with Herceptin and radiation therapy.

Tykerb may also increase the activity of other therapies used for HER2-positive metastatic breast cancer patients. Currently, the combination of Herceptin and Taxol (paclitaxel) is a standard-of-care for initial therapy in these patients. CORT is conducting a study that compares that standard treatment of Herceptin and Taxol with or without the addition of Tykerb.

For more information about these studies, visit or contact a Research Coordinator at 972-566-5588.