Adding Perjeta to Herceptin and Chemotherapy After Surgery Shows Benefits in Early-Stage HER2-Positive Breast Cancer

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Updated results from the APHINITY trial confirmed that adding Perjeta (chemical name: pertuzumab) to Herceptin (chemical name: trastuzumab) and chemotherapy after surgery for early-stage HER2-positive breast cancer reduces the risk of recurrence (the cancer coming back) and slightly improves survival.

The research was presented on Dec. 11, 2019, at the San Antonio Breast Cancer Symposium. Read the abstract of “Interim overall survival analysis of APHINITY (BIG 4-11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer.”

About Perjeta and Herceptin

Both Perjeta and Herceptin are targeted therapy medicines that treat HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals. While the medicines’ results are the same, they work in slightly different ways. Both Herceptin and Perjeta are given intravenously, which means they’re delivered directly into your bloodstream through an IV or a port.

About the APHINITY study

The APHINITY trial started in 2011, when the standard of care after surgery for early-stage HER2-positive breast cancer was Herceptin and chemotherapy. Based on early results from the APHINITY trial published in 2017, which showed that adding Perjeta to Herceptin and chemotherapy slightly improved survival, the standard of care for most stage II to stage III HER2-positive breast cancers became Herceptin, Perjeta, and chemotherapy after surgery.

In the APHINITY 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 and placebo plus chemotherapy (2,405 women)
  • Herceptin and Perjeta plus chemotherapy (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.

The 2019 results came after about 6 years of follow-up:

  • 90.6% of women treated with Herceptin, Perjeta, and chemotherapy were alive with no cancer recurrence
  • 87.8% of women treated with Herceptin and chemotherapy were alive with no cancer recurrence

Similar to the 2017 results, the 2019 results showed that women with breast cancer that had spread to the lymph nodes got the most benefits from adding Perjeta to Herceptin and chemotherapy. For women diagnosed with node-positive early-stage HER2-positive breast cancer:

  • 87.9% of women treated with Herceptin, Perjeta, and chemotherapy were alive with no cancer recurrence
  • 83.4% of women treated with Herceptin and chemotherapy were alive with no cancer recurrence

Still, overall survival — how long the women lived whether or not the cancer came back — was only slightly better for women treated with Perjeta, Herceptin, and chemotherapy:

  • 94.8% of women treated with Perjeta, Herceptin, and chemotherapy were alive after 6 years
  • 93.9% of women treated with Herceptin and chemotherapy were alive after 6 years

This difference was not statistically significant, which means that it could have happened by chance and not because of the difference in treatment.

“Following this interim analysis, the evidence is now even stronger that adding pertuzumab to the previous standard of care reduces the risk of disease recurrence for patients with HER2-positive breast cancer,” said Martine Piccart, M.D., scientific director at the Institut Jules Bordet in Brussels, who presented the results. “Altogether, the clinical benefit of pertuzumab, which is exemplified by its treatment effect against breast cancer and its lack of additional significant side effects, is enhanced for women at high risk of breast cancer recurrence in this curative setting.

“A main limitation of APHINITY is that although we have seen fewer deaths among the patients who received treatment with pertuzumab, our data is still immature and have not shown definitive improvement in overall survival,” she continued. “A longer follow-up is needed to see any significant survival benefit.”

Cardiac side effects

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:

  • 0.8% of women treated with Perjeta, Herceptin, and chemotherapy had heart failure
  • 0.3% of women treated with Herceptin and chemotherapy had heart failure

“Incidence of primary cardiac events remains less than 1% in both arms, providing further evidence that adding pertuzumab to trastuzumab and chemotherapy is safe in the long term,” Piccart said.

What this means for you

These results show that adding Perjeta to Herceptin and chemotherapy after surgery for early-stage HER2-positive disease offers more benefits than Herceptin and chemotherapy alone.

Still, recommended treatment for early-stage HER2-positive breast cancer currently is neoadjuvant treatment, which means chemotherapy and Herceptin and Perjeta are given before surgery. If any cancer is found during surgery after neoadjuvant treatment, Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) is usually recommended after surgery.

Still, if neoadjuvant treatment wasn’t recommended for you, these results from the APHINITY trial offer reassurance that adding Perjeta to Herceptin and chemotherapy after surgery is the best treatment for most people.

For more information on Perjeta, Herceptin, and other anti-HER2 medicines, visit the Breastcancer.org Targeted Therapies pages.

To talk with others diagnosed with HER2-positive breast cancer, join the Breastcancer.org Discussion Board forum HER2+ (Positive) Breast Cancer.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical advisor


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