The targeted therapy Perjeta (chemical name: pertuzumab), when used in combination with the targeted therapy Herceptin (chemical name: trastuzumab) and the chemotherapy Taxotere (chemical name: docetaxel) before breast cancer surgery, has been shown to improve survival in women diagnosed with high-risk, early-stage HER2-positive breast cancer.
Perjeta, also in combination with Herceptin and Taxotere, also has been shown to improve survival in women diagnosed with HER2-positive metastatic breast cancer. Metastatic breast cancer is cancer that has spread away from the breast to another part of the body, such as the bones or liver.
So doctors wondered if adding Perjeta to the standard treatment of Herceptin and chemotherapy after surgery could offer more benefits to women diagnosed with early-stage, HER2-positive breast cancer. Doctors call treatments given after surgery “adjuvant” treatments.
Early results from a study suggest that adding Perjeta to Herceptin and chemotherapy after surgery to treat early-stage, HER2-positive breast cancer slightly improves survival; women diagnosed with high-risk, HER2-positive, early-stage disease got more benefits.
The research was presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5, 2017 and published online on June 5, 2017 by The New England Journal of Medicine:
- Read the ASCO Annual Meeting abstract of “APHINITY trial (BIG 4-11): A randomized comparison of chemotherapy (C) plus trastuzumab (T) plus placebo (Pla) versus chemotherapy plus trastuzumab (T) plus pertuzumab (P) as adjuvant therapy in patients (pts) with HER2-positive early breast cancer (EBC).”
- Read The New England Journal of Medicine abstract of “Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.”
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.
In the APHINITY (A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 [HER2]-Positive Primary Breast Cancer) trial, 4,805 women diagnosed with early-stage, HER2-positive breast cancer had surgery to remove the breast cancer. The women were then randomly assigned to one of two treatment regimens after surgery:
- Herceptin plus chemotherapy and placebo (standard treatment) (2,405 women)
- Herceptin plus chemotherapy and Perjeta (Perjeta treatment) (2,400 women)
The placebo, a solution that contained no medicine, was given intravenously with the Herceptin and chemotherapy, so none of the women knew which treatment group they were in.
- About 63% of the women in each treatment group had node-positive disease, meaning cancer cells had been found in their lymph nodes.
- About 36% of the women in each treatment group had hormone-receptor negative breast cancer.
After 3 years of follow-up, the researchers looked at the disease-free survival rates in each treatment group. Disease-free survival is how long the women lived without the cancer coming back (recurrence).
The disease-free survival rate was higher than expected in both groups:
- 94.1% of the women in the Perjeta treatment group were alive with no cancer recurrence
- 93.2% of the women in the standard treatment group were alive with no cancer recurrence
This very slight difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
The researchers then looked at disease-free survival rates of women with node-positive disease:
- 92.0% of women in the Perjeta treatment group were alive with no cancer recurrence
- 90.2% of women in the standard treatment group were alive with no cancer recurrence
This difference WAS statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
The researchers also looked at disease-free survival rates of women with HER2-positive, hormone-receptor negative disease:
- 92.8% of women in the Perjeta treatment group were alive with no recurrence
- 91.2% of the women in the standard treatment group were alive with no recurrence
This slight difference also wasn’t statistically significant.
Breast cancer that is hormone-receptor-negative and/or node-positive is considered to have a higher recurrence risk.
"It's always an issue with adjuvant treatment that if you report the early results, you don't have the full view on the efficacy," said lead author Gunter von Minckwitz, M.D., Ph.D., president of the German Breast Group. "But with the data we have right now, these results support the use more in the higher-risk patients: node-positive and hormone-receptor-negative."
Like most cancer treatments, Perjeta, Herceptin, and chemotherapy can cause side effects, some of them severe.
Both Perjeta and Herceptin can cause heart problems, but few women in each treatment group experienced those side effects. Still, women in the Perjeta treatment group were slightly more likely to have heart problems:
- 0.7% of women in the Perjeta treatment group had heart failure
- 0.4% of women in the standard treatment group had heart failure
Diarrhea was the most severe side effect in both treatment groups and happened almost always during chemotherapy treatment:
- 9.8% of women in the Perjeta treatment group had severe diarrhea
- 3.7% of women in the standard treatment group had severe diarrhea
"…In the larger picture, we have to see who is this trial actually going to apply to," Leif William Ellisen, M.D., Ph.D., of the Massachusetts General Hospital Cancer Center, said in an interview. "The fact that differences were small and that these are very expensive drugs that do cause some additional toxicity suggests that this regimen might be better suited for higher risk patients, including those who have estrogen-receptor-negative disease and those who have node-positive disease. This will be fleshed out as we get more information on the study as the years go by."
While these results are promising, they are early results. As more data are collected, we will have a better idea of who will benefit the most from adding Perjeta to standard therapy after surgery for HER2-positive, early-stage breast cancer.
Still, if you have been diagnosed with early-stage, HER2-positive breast cancer that is considered to have a high risk of recurrence because the cancer is node-positive and/or hormone-receptor-negative, you may want to talk to your doctor about this study. Together, you can decide if adding Perjeta to your adjuvant treatment regimen makes sense for your unique situation.
For more information on Perjeta and Herceptin and their side effects, visit the Breastcancer.org Targeted Therapies section.
Editor’s Note: On Dec. 20, 2017, the U.S. Food and Drug Administration approved using Perjeta in combination with Herceptin and chemotherapy after surgery to treat HER2-positive, early-stage breast cancer with a high risk of recurrence.
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