Results from the MARIANNE study show that Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), a targeted therapy medicine, wasn’t better than the targeted therapy Herceptin (chemical name: trastuzumab) plus a taxane chemotherapy medicine as the first treatment for locally advanced or metastatic, HER2-positive breast cancer. Still, Kadcyla caused fewer side effects than Herceptin plus a taxane and offered the women better quality of life.
Herceptin plus taxane chemotherapy is the standard of care as a first treatment for locally advanced or metastatic, HER2-positive breast cancer.
The research was published in the January 2017 issue of the Journal of Clinical Oncology. Read the abstract of “Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Postive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.”
Kadcyla is a combination of Herceptin (chemical name: trastuzumab) and the chemotherapy medicine emtansine. In Kadcyla, the emtansine is attached to the Herceptin. In earlier studies on Kadcyla, it was reported that the chemotherapy medicine maytansine was attached to Herceptin to form Kadcyla. Emtansine is a derivative of maytansine.
Kadcyla is approved by the U.S. Food and Drug Administration (FDA) to treat HER2-positive, metastatic breast cancer that has previously been treated with Herceptin and a taxane chemotherapy.
Herceptin is approved by the FDA to treat advanced-stage, HER2-positive breast cancers and to lower the risk of recurrence of early-stage, HER2-positive breast cancer with a high risk of recurrence. 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. Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals.
Emtansine, like some other chemotherapy medicines, disrupts the way cells grow. Emtansine isn’t a targeted medicine, which means it can affect healthy cells as well as cancer cells.
Kadcyla was designed to deliver emtansine to cancer cells in a targeted way by attaching emtansine to Herceptin. Herceptin then carries emtansine to the HER2-positive cancer cells.
Locally advanced cancer is breast cancer that has spread to tissue near the breast, but not to parts of the body away from the breast. Metastatic breast cancer is cancer that has spread to parts of the body away from the breast, such as the bones or liver.
In the MARIANNE study, researchers wanted to know if Kadcyla was better than Herceptin and a taxane as the first treatment for advanced-stage, HER2-positive disease.
In the study, the researchers randomly assigned 1,095 women diagnosed with locally advanced or metastatic, HER2-positive breast cancer to one of three treatments as the first treatment for the disease:
- Herceptin plus taxane chemotherapy (365 women)
- Kadcyla plus Perjeta (chemical name: pertuzumab) (363 women)
- Kadcyla alone (367 women)
All three treatments were given intravenously, which means they were delivered directly into the bloodstream through an IV or a port.
The researchers wanted to see which treatment offered the longest progression-free survival. Progression-free survival is how long the women lived without the cancer growing.
The women were followed for about 3 years.
Progression-free survival was:
- 13.7 months for Herceptin plus a taxane
- 14.1 months for Kadcyla
- 15.2 months for Kadcyla and Perjeta
None of the differences in progression-free survival times were statistically significant, which means they could have been due to chance and not because of the difference in treatments.
Like almost all cancer treatments, Herceptin, taxane chemotherapy, Kadcyla, and Perjeta can cause side effects, some of them serious.
In this study, women treated with Herceptin plus taxane chemotherapy had more serious side effects than women treated with Kadcyla:
- 54.1% of women treated with Herceptin plus a taxane had a serious side effect
- 45.4% of women treated with Kadcyla alone had a serious side effect
- 46.2% of women treated with Kadcyla plus Perjeta had a serious side effect
The most common serious side effects in women treated with Herceptin and a taxane were:
- low white blood cell counts
The most common serious side effects in women treated with Kadcyla or Kadcyla plus Perjeta were:
- increased blood levels of an enzyme that can signal liver or heart damage
- low platelet counts
- low red blood cell counts
Women treated with Herceptin and a taxane had more overall side effects. The most common side effects and their rates were:
- 59.8% of women in the Herceptin plus taxane group
- 9.0% of women in the Kadcyla plus Perjeta group
- 6.6% of women in the Kadcyla alone group
- 48.7% of women in the Herceptin plus taxane group
- 48.1% of women in the Kadcyla plus Perjeta group
- 25.2% of women in the Kadcyla alone group
- peripheral neuropathy
- 28.0% of women in the Herceptin plus taxane group
- 17.8% of women in the Kadcyla plus Perjeta group
- 13.3% of women in the Kadcyla alone group
Still, there were certain side effects that were more common in women treated with Kadcyla compared to women treated with Herceptin and a taxane, including nausea, headache, and bloody noses.
The researchers concluded that treatment regimens that included Kadcyla weren’t less effective than the regimen of Herceptin plus a taxane. But the Kadcyla regimens also weren’t more effective than the current standard of care. The researchers also suggested that because Kadcyla regimens seem to be better tolerated than Herceptin and a taxane, a Kadcyla regimen may be a good alternative treatment option for women diagnosed with metastatic, HER2-positive breast cancer who aren’t considered suitable for the standard treatment because of other health conditions.
If you’ve been diagnosed with advanced-stage, HER2-positive breast cancer, you and your doctor are likely considering a number of treatment options. If you have other medical conditions, such as a history of heart problems, that might make Herceptin a less desirable choice for you, you may want to ask your doctor about this study and whether Kadcyla would be a good fit for your unique situation.
For more information, visit the Breastcancer.org Kadcyla pages.
Editor's Note: On May 3, 2019, the FDA approved Kadcyla to treat early-stage HER2-positive breast cancer after surgery if residual disease was found after neoadjuvant treatment with taxane chemotherapy and Herceptin.