In June 2012, the U.S. Food and Drug Administration (FDA) approved using the targeted therapy medicine Perjeta (chemical name: pertuzumab) in combination with Herceptin (chemical name: trastuzumab) and Taxotere (chemical name: docetaxel) to treat HER2-positive, metastatic breast cancer that hasn’t been treated with either Herceptin or chemotherapy yet. (Perjeta was called Omnitarg in earlier studies.)
Metastatic breast cancer is cancer that has spread to parts of the body away from the breast, such as the bones or liver.
The FDA approval was based on results from the CLEOPATRA (Clinical Evaluation Of Pertuzumab And TRAstuzumab) study. The study showed that women diagnosed with metastatic, HER2-positive breast cancer who were treated with a combination of Perjeta, Herceptin, and Taxotere lived 6 months longer without the cancer growing (progression-free survival) compared to women treated with only Herceptin and Taxotere.
On June 21, 2012, Genentech, the company that makes Perjeta, announced that more results from the CLEOPATRA study showed that women who got Perjeta, Herceptin, and Taxotere had better overall survival (the time a woman lives with or without the cancer growing) than women who got only Herceptin and Taxotere.
On Sept. 28, 2014, final results from the CLEOPATRA study showed that women who got Perjeta, Herceptin, and Taxotere lived about 1.5 years longer than women who got only Herceptin and Taxotere.
The results were presented at the 2014 European Society for Medical Oncology meeting and also released by Genentech.
Read the abstract of “Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC).”
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 cancers that are HER2-negative. Both Herceptin and Perjeta work against HER2-positive breast cancers by blocking the cancer cells' ability to receive growth signals. Both medicines are given intravenously, which means they’re delivered directly into your bloodstream though an IV or a port. A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.
Herceptin, also a targeted therapy medicine, is FDA-approved to treat advanced-stage, HER2-positive breast cancer and to lower the risk of recurrence (the cancer coming back) of early-stage, HER2-positive breast cancer with a high risk of recurrence.
Earlier research suggested that Perjeta could boost Herceptin’s ability to weaken or destroy HER2-positive breast cancers. So the CLEOPATRA study looked to see how the two medicines could be used together to treat HER2-positive breast cancer. Doctors sometimes call the Herceptin-Perjeta combination “dual HER2 antibody therapy.”
In the CLEOPATRA study, 808 women diagnosed with HER2-positive, metastatic breast cancer that hadn't been treated yet were randomly assigned to receive one of two treatment regimens:
- half the women got Herceptin, Taxotere, and Perjeta
- half the women got Herceptin, Taxotere, and a placebo infusion (instead of Perjeta)
More than 80% of women who got Herceptin, Taxotere, and Perjeta had some response to the treatment compared to 69% of women who got only Herceptin and Taxotere.
The final overall survival results showed that women who were treated with Perjeta, Herceptin, and Taxotere lived about 5 years (56.5 months). Women who got only Herceptin and Taxotere lived for about 3.5 years (40.8 months).
“The 56.5-month median overall survival is unprecedented in this indication, as is the 15.7-month improvement in median survival,” said Sandra Swain, M.D., of MedStar Washington Hospital Center in Washington, D.C., who was the lead author of the study. “The outcome confirms the pertuzumab regimen as first-line standard of care for patients with HER2-positive metastatic breast cancer.”
There was only a small increase in side effects in women treated with Herceptin, Taxotere, and Perjeta compared to women who got only Herceptin and Taxotere.
The most common serious side effects in both treatment groups were low white blood cell counts (called neutropenia), with or without fever. Problems with heart function or developing heart failure can sometimes be side effects of both Herceptin and Perjeta. The CLEOPATRA study found that adding Perjeta didn’t increase the risk of heart problems.
“Based on the CLEOPATRA data, we solidified the notion that, for patients eligible to receive first-line treatment, for HER2-positiive metastatic breast cancer, patients should receive a triplet of chemotherapy in combination with trastuzumab and pertuzumab,” said Edith Perez, M.D., director of the breast program at the Mayo Clinic and member of the Breastcancer.org Professional Advisory Board.
If you’ve been diagnosed with HER2-positive metastatic breast cancer and haven’t started treatment yet, it’s a good idea to ask your doctor about this study and whether the combination of Perjeta, Herceptin, and Taxotere makes sense for your unique situation.
Editor’s Note: This article was updated with information about Herceptin Hylecta, which the FDA approved on Feb. 28, 2019.