Large Study Confirms Trastuzumab More Effective Than Lapatinib

Breast Cancer News
December 11, 2014
Erin Rowley, Writer and Content Coordinator
Reviewed By: 
Chau T. Dang, MD

At the European Society for Medical Oncology 2014 Congress, in Madrid, in late September, Researchers presented expanded results from the ALTTO trial. These results show trastuzumab alone is more effective than lapatinib alone for early-stage, HER2-positive breast cancer.

Background and Goals

More than 8,000 people from over 40 countries participated in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial. The study looked at HER2-positive breast cancer, which grows because of too many human epidermal growth factor receptor 2 proteins on breast cells. 

Trastuzumab (Herceptin) is a monoclonal antibody that targets cancer cells that contain extra copies of the HER2 gene. It is the standard adjuvant treatment for this type of breast cancer, meaning it’s given after surgery. Another HER2 medicine, lapatinib, (Tykerb) blocks the activity of the HER2 protein. It is FDA-approved for metastatic breast cancer, but not for early-stage.

Other results from ALTTO that were released earlier this year showed taking lapatinib and trastuzumab at the same time was not better than trastuzumab alone. They also showed that giving trastzumab first and then switching to lapatinib was not as good as trastuzumab alone. Combining the medicines did, however, increase side effects.


For the part of the ALTTO trial that compared trastuzumab alone and lapatinib alone, 4,197 people who had already been treated with surgery and chemotherapy were randomly put in one of two groups.

  • One group received trastuzumab by IV once a week or once every 3 weeks for 1 year.
  • The other group was assigned to receive lapatinib as a pill once a day for 1 year.

Researchers measured disease-free survival (DSF), the length of time after starting treatment without a new cancer forming or cancer returning.


After a median 4.5 years, one or more disease events, meaning a new or returning breast cancer or death from any cause, happened in

  • 17 percent of the lapatinib group
  • 14 percent of the trastuzumab group

Side effects were seen more often in people taking lapatinib.

Because of the significant difference in DFS, the lapatinib-only arm was closed early and those participants were allowed to switch to trastuzumab. More than half of them did that, and it appears that receiving trastuzumab benefited those people.

What This Means for You

ALTTO shows lapatinib isn’t as effective as trastuzumab in treating early-stage, HER2-positive breast cancer. Researchers now have little interest in continuing to study lapatinib in this group of people. If you have early-stage, HER2-positive breast cancer you may feel disappointed at these results. But lapatinib, and any other medicine for HER2-positive breast cancer, is always going to have an uphill battle, because it’s being tested against a very effective medicine that’s already widely available – trastuzumab.

If you’re someone for whom trastuzumab isn’t working well, this study does not mean there’s no hope for you. Promising medicines, including cancer vaccines that help your immune system fight the disease, pertuzumab (Perjeta) which, like trastuzumab, is a monoclonal antibody, and T-DM1 (Kadcyla), which combines trastuzumab with another medicine, are being studied now. If you want a chance to receive new medicines like these, look at and talk to your doctor to see if you’re eligible for a clinical trial.

Perez, Edith A.; Holmes, Eileen; de Azambuja, Evandro. Disease-free survival (DFS) in the lapatinib alone arm and expanded results of the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) in the adjuvant treatment of HER2-positive early breast cancer (EBC). Presented at the European Society for Medical Oncology 2014 Congress; September 29, 2014; Madrid, Spain.

Additional Related Topics 
Clinical Trials