Neratinib Plus Capecitabine Shows Promise in HER2-Positive Metastatic Breast Cancer Study

Breast Cancer News
April 14, 2015
Erin Rowley, Writer and Content Coordinator
Reviewed By: 
Ruth Oratz, MD, FACP

A small, stageinfo-icon I/II study found that giving the anti-cancer medicines neratinib and capecitabineinfo-icon at the same time may help people with HER2-positive metastaticinfo-icon breast cancer that is no longer responding to standard treatment.

Background and Goals

Breast cancer is HER2-positive when a tumorinfo-icon grows because too many human epidermal growth factor receptor 2info-icon proteins cause cells to multiply more quickly than normal. About 20 percent of breast cancers are considered HER2-positive. Breast cancer can also be metastatic, meaning it has spread outside of the breast and lymphinfo-icon nodes.

FDAinfo-icon-approved medicines for HER2-positive metastatic breast include trastuzumabinfo-icon (Herceptininfo-icon), pertuzumabinfo-icon (Perjeta), T-DM1 (Kadcyla) and lapatinibinfo-icon (Tykerbinfo-icon). But sometimes cancer can continue to grow despite use of these treatments. Neratinib and capecitabine (Xelodainfo-icon) are two treatments currently under study that have shown promise in treating HER2-positive metastatic breast cancer that isn’t responding to standard therapyinfo-icon.

The researchers gave the two medicines together to people with metastatic HER2-positive breast cancer in order to answer two important questions:

  • What is the maximum doseinfo-icon of neratinib plus capecitabine that people can tolerate?
  • How safe and effective is neratinib plus capecitabine for treating people with HER2-positive metastatic breast cancer?


To find out how much of the medicines could be given to people without side effects becoming too dangerous or too uncomfortable, the researchers recruited participants who had solid tumors – associated with any type of cancer, not just breast cancer – and whose disease was not responding to standard treatments. Participants were given different doses of the medicines, starting with low doses and gradually building up to higher doses. The highest dose at which just 1 of 6 or 2 of 9 participants needed their dose adjusted because of side effects was considered the maximum dose that could be tolerated. This first step involved 33 participants.

To find out how safe and effective the medicines were, researchers then gave this treatment to 72 more people with HER2-positive metastatic breast cancer that had progressed despite past treatment with trastuzumab and a type of chemotherapyinfo-icon called a taxaneinfo-icon, using the dose decided upon in the first step. Sixty-five of the participants had been treated with lapatinib in the past; seven had not. Researchers measured objective responseinfo-icon rate, ORR, the number of participants in which the cancer decreased in size or disappeared after treatment; progression-free survivalinfo-icon, PFS, the time from start of treatment to disease growth; and overall survival, OS, the time from the start of treatment to death.


The highest dose that could be safely given was 240 mg of neratinib once a day (the same recommended dose as when neratinib is used alone) plus 1,500 mg of capecitabine two times a day.

Overall, more than half of participants saw the cancer shrink or disappear after treatment with neratinib and capecitabine. Participants who had not been treated with lapatinib in the past had the most benefit:

  • ORR of 64 percent
  • medianinfo-icon PFS of 40.3 weeks

Participants who had been treated with lapatinib in the past also had strong responses:

  • ORR of 57 percent
  • median PFS of 35.9 weeks

The most common side effects were

  • diarrheainfo-icon, experienced by 88 percent of participants
  • hand-foot syndrome, redness, swelling and pain on the palms of the hands or the soles of the feet, experienced by 48 percent of participants

Levels of hand-foot syndrome in this trial were similar, but levels of diarrhea were significantly higher, compared to those seen in studies of capecitabine alone.


Because this is a phase I/II trialinfo-icon, it involved a small number of participants. A phase III trialinfo-icon, called NALA, is comparing neratinib plus capecitabine to lapatinib plus capecitabine. This trial is currently recruiting participants.

What This Means for You

Trastuzumab and pertuzumab have extended life for many people with HER2-positive breast cancer. But if you have breast cancer that has grown or spread despite treatment with this or other medicines, you may feel disappointed and frustrated. However, HER2-positive metastatic disease is being actively studied in breast cancer research. You can take comfort in knowing that doctors are constantly testing new medicines or combining existing medicines to find new ways to treat this type of breast cancer.

If you’re interested in participating in the NALA trial or other clinicalinfo-icon trials, talk to your doctor and look at

Saura, Cristina; Garcia-Saenz, Jose A.; Xu, Binghe. Safety and Efficacy of Neratinib in Combination With Capecitabine in Patients With Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Journal of Clinical Oncologyinfo-icon. Volume 32, no. 32 3626-3633, November 10, 2014; doi: 10.1200/JCO.2014.56.3809.

You must have Javascript enabled to use this form.

More In Targeted Therapy

Additional Related Topics 
Clinical Trials