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Combo of Tykerb, Herceptin, and Aromatase Inhibitor Seems Best for Metastatic, HER2-Positive, Hormone-Receptor-Positive Disease

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A study has found that a combination of Tykerb (chemical name: lapatinib), Herceptin (chemical name: trastuzumab), and an aromatase inhibitor is better than just Herceptin and an aromatase inhibitor or just Tykerb and an aromatase inhibitor for treating metastatic HER2-positive, hormone-receptor-positive breast cancer in postmenopausal women.

The research was published online on Dec. 15, 2017 by the Journal of Clinical Oncology. Read the abstract of “Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE.”

HER2-positive cancers have too many copies of the HER2 gene, which make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that encourage the cancer to grow and spread. About one out of every four breast cancers is HER2-positive.

Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals. Herceptin is given intravenously. Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk) is an injectable form of Herceptin.

Like Herceptin, Tykerb works against cancers that are HER2-positive. Tykerb works by blocking the HER2 protein’s ability inside the cell to make HER2-positive breast cancers grow. Tykerb is a pill taken by mouth.

The aromatase inhibitors are a type of hormonal therapy medicine used to treat hormone-receptor-positive breast cancer. They work by lowering the amount of estrogen in the body and by blocking the action of estrogen on breast cancer cells. There are three aromatase inhibitors:

  • Arimidex (chemical name: anastrozole)
  • Aromasin (chemical name: exemestane)
  • Femara (chemical name: letrozole)

All the aromatase inhibitors are pills taken by mouth.

Most women diagnosed with metastatic HER2-positive breast cancer are treated with some type of anti-HER2 medicine and chemotherapy as a first treatment, no matter the hormone receptor status of the cancer. Using two anti-HER2 medicines plus chemotherapy has been shown to be more effective and has become the standard of care for metastatic HER2-positive disease. Still, not all people diagnosed with metastatic HER2-positive, hormone-receptor-positive breast cancer need or can tolerate chemotherapy. So, doctors wondered if two anti-HER2 medicines plus hormonal therapy would be effective.

This study, called the ALTERNATIVE trial, included 353 women who had been diagnosed with metastatic HER2-positive, hormone-receptor-positive breast cancer. Before joining this study, all the women had been treated with hormonal therapy as well as Herceptin and chemotherapy.

The women were randomly split into three treatment groups:

  • 118 women were treated with Tykerb, Herceptin, and an aromatase inhibitor
  • 116 women were treated with Herceptin and an aromatase inhibitor
  • 119 women were treated with Tykerb and an aromatase inhibitor

The aromatase inhibitor used was chosen by the women’s doctors:

  • 47% of the women were treated with Aromasin
  • 42% were treated with Femara
  • 11% were treated with Arimidex

The researchers wanted to know if the combination of Tykerb, Herceptin, and an aromatase inhibitor would offer better progression-free survival than the other two treatment combinations.

Progression-free survival is how long a person lives without the cancer growing.

Overall, progression-free survival was better in the women treated with Tykerb, Herceptin, and an aromatase inhibitor. Progression-free survival was:

  • 11 months for women treated with Tykerb, Herceptin, and an aromatase inhibitor
  • 5.7 months for women treated with Herceptin and an aromatase inhibitor
  • 8.3 months for women treated with Tykerb and an aromatase inhibitor

Like most cancer medicines, Tykerb, Herceptin, and the aromatase inhibitors can cause side effects, some of them severe. In this study, the most common side effects were:

  • diarrhea
  • rash
  • nausea
  • infection in the finger or toe nails

The percentage of women who stopped treatment because of side effects was:

  • 3% (4 women) in the Tykerb-Herceptin-aromatase inhibitor arm
  • 6% (7 women) in the Herceptin-aromatase inhibitor arm
  • 9% (11 women) in the Tykerb-aromatase inhibitor arm

“Our study demonstrated that the combination of Tykerb plus Herceptin plus aromatase inhibitor provided a clinically meaningful prolongation of progression-free survival compared with Herceptin plus aromatase inhibitor, representing a statistically significant 38% reduction in the risk of disease progression,” the researchers wrote. “This combination can potentially offer an effective and well-tolerated, chemotherapy-sparing alternative treatment regimen for patients for whom chemotherapy is not intended.”

If you’ve been diagnosed with metastatic HER2-positive, hormone-receptor-positive breast cancer, you and your doctor will consider a number of treatment options. If you’re not a good candidate for chemotherapy, you may want to talk to your doctor about this study.

It’s important to remember that while there are many standard regimens to treat metastatic breast cancer, each person’s treatment plan will be unique because each cancer is unique. Besides the characteristics of the cancer, your doctor also will take into account other health issues you may have, including heart problems, high blood pressure, and diabetes. These and other conditions can affect which medicines your doctor recommends for you.

For more information on Herceptin and Tykerb, visit the Targeted Therapies pages. For more information on the aromatase inhibitors, visit the Hormonal Therapy pages.

Editor’s Note: This article was updated with information about Herceptin Hylecta, which the U.S. Food and Drug Administration (FDA) approved on Feb. 28, 2019.

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