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Experimental Medicine Neratinib Helps Treat Early-Stage, HER2-Positive Disease

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A study suggests that the experimental targeted therapy neratinib can improve disease-free survival when given after surgery, chemotherapy, and Herceptin (chemical name: trastuzumab) to treat early-stage, HER2-positive breast cancer.

The study was published online on Feb. 10, 2016 by The Lancet Oncology. Read the abstract of “Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.”

HER2-positive breast cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive and harder to treat than HER2-negative breast cancers.

Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals. Herceptin, which is given intravenously, is approved by the U.S. Food and Drug Administration (FDA) to:

  • treat advanced-stage, HER2-positive breast cancers
  • be given to women with earlier stages of HER2-positive disease as adjuvant treatment (treatment after initial treatment, such as surgery) either alone or as part of a regimen with chemotherapy

A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.


Neratinib is a type of targeted therapy medicine called an irreversible pan-HER inhibitor. Neratinib fights HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals. Neratinib is a pill taken by mouth.

Disease-free survival is how long a woman lives without the cancer growing.

Phase I and phase II studies done earlier suggested that neratinib may help treat HER2-positive breast cancer. Phase I and phase II studies focus on dose amounts and safety.

This study, called ExteNET, was a phase III study. Phase III studies compare the safety and effectiveness of a new treatment to the current standard of care and are usually much larger than phase I and phase II studies.

The study included 2,840 women diagnosed with early-stage, HER2-positive breast cancer that had been treated with Herceptin and chemotherapy before and after surgery. The women had completed Herceptin and chemotherapy treatment up to 2 years before the study started. The women were randomly assigned to get one of two treatments for 12 months:

  • 1,420 women got neratinib
  • 1,420 women got a placebo (a sugar pill that looked just like neratinib)

After about 2 years of follow-up:

  • 70 women who got neratinib had the cancer come back (a recurrence)
  • 109 women who got placebo had a recurrence

This difference was statistically significant, which means that it was likely because of the difference in treatment and not just due to chance.

The 2-year disease-free survival rates were:

  • 93.9% for women who got neratinib
  • 91.6% for women who got placebo

Like almost all cancer treatments, neratinib can cause side effects, some of them serious.

This study found that diarrhea, vomiting, and nausea -- sometimes severe -- were more common in women who got neratinib compared to women who got placebo.

While the results of this study are encouraging, they look at only 2 years of follow-up. The researchers recommended longer follow-up to make sure that the benefits of neratinib last over time.

If you’ve been diagnosed with early-stage, HER2-positive breast cancer and are planning your treatments after surgery, you may want to ask your doctor about this study. If you’re willing to participate in a clinical trial, you may have the option of being treated with neratinib after Herceptin and chemotherapy, if it makes sense for your unique situation. Talk to your doctor about clinical trials that might be a good fit for you. You can visit the Clinical Trials pages for more information.

And stay tuned to’s Research News for the latest information on neratinib.

Editor’s Note: On July 17, 2017, the U.S. Food and Drug Administration approved Nerlynx (chemical name: neratinib) to treat early-stage, HER2-positive breast cancer for an extended period after surgery in people who have previously been treated with Herceptin (chemical name: trastuzumab).

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

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