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Trial Examines Optimal Treatments for HER2-Positive Early Breast Cancer

Phase III trial will compare lapatinib and trastuzumab in preventing recurrence after surgery and chemotherapy

Trial Starts: 6/1/2007

Written By Mary Alice Hartsock
Reviewed By Kathy D. Miller, MD

A new international clinical trial is seeking 8,000 women with HER2-positive, early breast cancer to determine whether lapatinib (Tykerb) after surgery and chemotherapy is more effective than trastuzumab (Herceptin) in preventing recurrence and extending survival.

The Phase III trial, called Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation, or ALTTO, is the first major trial to test whether lapatinib, which is approved for HER2-positive advanced (metastatic) breast cancer, may also be effective for early-stage breast cancer when given after surgery and chemotherapy. The researchers hope the trial may determine the standard of care for women with HER2-positive early breast cancer.

"Women diagnosed with HER2+ breast cancer today enjoy a much better prognosis with the addition of trastuzumab to adjuvant chemotherapy," says Kathy D. Miller, MD. "This study hopes to further improve on those results and will test which method of inhibiting HER2 is the more effective."

Understanding HER2, Lapatinib and Trastuzumab

HER2, also called human epidermal growth factor receptor 2, is a protein found on the surface of cells. In some breast cancers, the HER2 gene becomes "amplified" or "overexpressed," producing extra copies of itself. Tumors that overexpress HER2 are aggressive and more likely than other tumors to recur or travel to other parts of the body.

Lapatinib is a targeted therapy that may prevent cancer growth by blocking the activity of the HER2 protein. The U.S. Food and Drug Administration has approved lapatinib only for advanced breast cancer.

Trastuzumab is a monoclonal antibody, or a substance produced in a laboratory that can locate and attach to certain proteins or deliver medications directly to a breast tumor. Trastuzumab targets cancer cells that contain extra copies of the HER2 gene. Trastuzumab is FDA approved for both early-stage and advanced breast cancer.

Goals of the ALTTO Trial

This trial has two primary goals:

  • To find out how effective lapatinib is in preventing cancer from returning in people with HER2 positive early breast cancer.
  • To assess lapatinib’s ability to extend survival in people with HER2 positive early cancer.

Other goals are:

  • To test lapatinib’s safety and examine its side effects.
  • To learn whether biomarkers can be used to predict whether lapatinib will prevent recurrence. Biomarkers are substances found in the blood, body fluids or tissues that at high levels can indicate the presence of a certain type of cancer.
  • To evaluate whether genetics can be used to determine how well you will respond to lapatinib.

ALTTO’s Structure

The ALTTO trial will randomly assign 8,000 people from 50 countries to one of four treatment arms:

  • Trastuzumab alone, given intravenously (by IV) once weekly or once every three weeks for 52 weeks.
  • Lapatinib alone, given as a pill once daily for 52 weeks.
  • Trastuzumab for 12 weeks, followed by a six-week break, followed by lapatinib for 34 weeks.
  • Lapatinib and trastuzumab together for 52 weeks.

Some people also will receive paclitaxel (Taxol) chemotherapy each week during the first 12 weeks.

Before starting the trial, participants will have already completed surgery and chemotherapy with an anthracycline (doxorubicin [Adriamycin] or epirubicin [Ellence]). They will be followed for ten years after the start of treatment.

Am I Eligible?

You may be eligible to participate in the ALTTO trial if you have been diagnosed with early breast cancer and:

  • You had one lump in your breast.
  • Your lump has been removed or will be removed surgically.
  • Your tumor is HER2-positive (ErbB2-positive).
  • You have received or are scheduled to receive at least four chemotherapy treatments containing an anthracycline.
  • You have not received trastuzumab or lapatinib.

You may need to have a physical exam and tests to examine your heart and blood to find out if you are eligible. A mammogram also may be required. If you are premenopausal, you may need a urine or blood test to make sure you aren’t pregnant.

What Else Do I Need to Know?

Since lapatinib has been studied in women with advanced breast cancer, doctors know more about how lapatinib affects the body than they know about some experimental medications. Common side effects include diarrhea, appetite loss, nausea, vomiting, rash and fatigue. Some people experience irregular heartbeat, shortness of breath or tingling in the hands and feet.

Through your participation, you could be making a significant contribution to breast cancer research and other women affected by breast cancer. This trial may help researchers establish a standard of care for people with HER2 positive early breast cancer, much like the clinical trials that discovered the effectiveness of raloxifene (Evista) and the aromatase inhibitors compared to tamoxifen for estrogen receptor-positive breast cancer. Your doctor can help you figure out whether you should participate.

For contact information, visit the website of the ALTTO trials.

Read more about this clinical trial.