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Herceptin Plus Tykerb After Surgery No Better Than Herceptin Alone for Early-Stage, HER2-Positive Disease

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Treatment given to weaken and destroy breast cancer BEFORE surgery is called neoadjuvant treatment. Treatment before surgery isn't routinely used to treat early-stage breast cancer, but may be used if the cancer is large or aggressive.

Treatment given to kill any few cancer cells that might remain AFTER surgery and reduce the risk of the cancer coming back (recurrence) is called adjuvant treatment.

In 2012, results from the NeoALTTO trial found that giving both Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib) with the chemotherapy medicine Taxol (chemical name: paclitaxel) before surgery to treat early-stage or locally advanced HER2-positive breast cancer offered more benefits than giving only Herceptin and Taxol or only Tykerb and Taxol.

Because of these encouraging results, researchers wanted to know if giving both Herceptin and Tykerb after surgery to remove early-stage, HER2-positive breast cancer would offer more benefits than only Herceptin or only Tykerb after surgery.

A study, called the ALTTO trial, has found that women diagnosed with early-stage, HER2-positive breast cancer who were treated with both Herceptin and Tykerb after surgery did no better than women who were treated with only Herceptin after surgery. The women who were treated with both Herceptin and Tykerb also had more side effects.

The research was published online on Nov. 23, 2015 by the Journal of Clinical Oncology. Read the abstract of “Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.”

Martine Piccart-Gebhart, M.D., Ph.D., associate professor of oncology at the Universite Libre de Bruxelles and member of the Professional Advisory Board, is the lead author of the study. Edith Perez, M.D., professor of medicine at the Mayo Clinic and also a member of the Professional Advisory Board, is another author.

HER2-positive breast cancers have too many copies of the HER2/neu gene, which make too much of the HER2 protein. HER2-positive breast cancers tend to be more aggressive than HER2-negative cancers. Herceptin and Tykerb are targeted therapies that fight against HER2-positive breast cancers by blocking the cancer cells' ability to receive growth signals.

Herceptin is given intravenously. Tykerb is a pill taken by mouth. A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.

In the ALTTO trial, 8,381 women from 44 countries diagnosed with early-stage, HER2-positive breast cancer that had been surgically removed were randomly assigned to get one of four anti-HER2 targeted therapy treatments for a year after surgery:

  • Herceptin alone
  • Tykerb alone
  • Herceptin for 12 weeks, a 6-week break, then 34 weeks of Tykerb
  • Herceptin and Tykerb given at the same time

The women’s doctors decided when they would get anti-HER2 therapies:

  • after all chemotherapy was completed
  • after anthracycline chemotherapy and at the same time as taxane chemotherapy
  • at the same time as the chemotherapy combination of Taxotere (chemical name: docetaxel) and carboplatin (this chemotherapy regimen is anthracycline-free; heart problems can be a side effect of Herceptin, Tykerb, and anthracycline chemotherapy)

The women joined the study between 2007 and 2011 and were followed for about 4.5 years.

The researchers wanted to see if treatment with both Herceptin and Tykerb would improve disease-free survival. Disease-free survival is how long the women lived before the cancer came back.

In 2011, the researchers did an early analysis of results and found that women being treated with Tykerb alone had shorter disease-free survival than women being treated with Herceptin alone. Herceptin after surgery for early-stage, HER2-positive disease is the treatment standard. So because Tykerb alone after surgery wasn’t as good as the standard, the researchers ended that treatment arm and women who had no recurrence were offered Herceptin alone.

The researchers found that women who were treated with Herceptin and Tykerb at the same time had slightly better disease-free survival than women treated with Herceptin alone. Women who were treated with Herceptin then Tykerb had an even smaller increase in disease-free survival compared to women treated with Herceptin alone.

Still, these differences weren’t statistically significant, which means that they could have been due to chance instead of the difference in treatments.

Women who were treated with Tykerb had more side effects and more serious side effects than women who were treated only with Herceptin, including:

  • diarrhea
  • neutropenia (low white blood cell count)
  • rash
  • liver problems

Also, women who were treated with Tykerb and Herceptin at the same time were more likely than women in the other treatment groups to stop treatment early because of side effects.

Many doctors were eagerly waiting for the results of this study because they thought the outcome would be very positive. Unfortunately, the results were disappointing.

The researchers said that 1 year of Herceptin after surgery remains the standard of care for women diagnosed with early-stage, HER2-positive breast cancer.

If you’ve been diagnosed with early-stage, HER2-positive breast cancer, it’s very likely that Herceptin will be part of your treatment plan after surgery. You and your doctor will consider the characteristics of the cancer, your unique situation, any other health issues you have, and your personal preferences when creating your treatment plan. Ask your doctor why Herceptin is or isn’t recommended for you after surgery and how that decision was made. Together, you can decide on the best treatment plan for your unique situation.

For more information, including how Herceptin works and possible side effects, visit the Herceptin pages.

Editor’s Note: This article was updated with information about Herceptin Hylecta, which the FDA approved on Feb. 28, 2019.

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