Experimental Margetuximab May Help Treat Certain HER2-Positive Metastatic Breast Cancers
The experimental targeted therapy margetuximab combined with chemotherapy may help treat pretreated metastatic HER2-positive breast cancer in people with a specific variant of CD16A, a protein that activates immune cells.
The experimental targeted therapy margetuximab combined with chemotherapy offered a slight improvement in progression-free survival compared to Herceptin (chemical name: trastuzumab) and chemotherapy for metastatic HER2-positive breast cancer that had been previously treated with anti-HER2 medicines, according to results from the SOPHIA study.
Still, the results also suggested that people with a specific variant of CD16A, a protein that activates immune cells, may get more benefits from margetuximab.
The research was presented on June 4, 2019, at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. Read the abstract of “SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx).”
Progression-free survival is how long the people in the study lived before the cancer grew.
Margetuximab is an experimental HER2 inhibitor targeted therapy. Margetuximab works by blocking the ability of HER2-positive cancer cells to receive chemical signals that tell them to grow. Margetuximab also was designed to improve the ability of immune cells to bind to HER2-positive breast cancer cells, allowing the immune cells to destroy the cancer cells.
About the SOPHIA study
Currently, the standard of care for first-line treatment for metastatic HER2-positive breast cancer is a combination of Herceptin, Perjeta (chemical name: pertuzumab), and chemotherapy. If the cancer continues to grow, Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) is used as a second-line treatment. There is no agreed-upon standard for third-line treatment if the cancer continues to grow, though anti-HER2 medicines combined with chemotherapy are commonly used.
According to Hope Rugo, M.D., clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, who presented the research, there are currently no approved medicines to treat metastatic HER2-positive breast cancer that has previously been treated with Herceptin, Perjeta, and Kadcyla. Rugo is also a member of the Breastcancer.org Professional Advisory Board.
“If margetuximab is approved … I believe that this agent could become a valuable treatment option for these patients,” Rugo said in a media release about the study.
The SOPHIA study included 536 people diagnosed with metastatic HER2-positive breast cancer that had been previously treated with one to three lines of therapy. All the people in the study had previously been treated with Herceptin and Perjeta, and more than 90% of the people had been treated previously with Kadcyla. About 15% had previously been treated with Tykerb (chemical name: lapatinib).
About half the people in the study were older than 55 and about half were younger.
The study participants were randomly assigned to the doctor’s choice of chemotherapy plus either margetuximab or Herceptin:
- 266 people were treated with margetuximab and chemotherapy
- 270 people were treated with Herceptin and chemotherapy
- 35% were treated with Navelbine (chemical name: vinorelbine)
- 27% were treated with Xeloda (chemical name: capecitabine)
- 25% were treated with Halaven (chemical name: eribulin)
- 12% were treated with Gemzar (chemical name: gemcitabine)
The results showed that the people treated with margetuximab and chemotherapy had a 24% lower risk of the cancer growing or death compared to people treated with Herceptin and chemotherapy.
Still, this only improved progression-free survival by less than a month. Progression-free survival was:
- 5.8 months for people treated with margetuximab and chemotherapy
- 4.9 months for people treated with Herceptin and chemotherapy
CD16A protein type affects margetuximab’s benefits
The CD16A protein sits on the surface of certain immune cells. When it receives signals from other cells, it activates the immune system cells to start destroying cells identified as invaders in the body.
People can have different forms of the CD16A protein, called alleles. CD16A alleles include CD16A-FF, CD16A-FV, and CD16A-VV.
According to Rugo, most people diagnosed with breast cancer have either the CD16A-FV (40% to 45%) or the CD16A-FF allele (about 40%). About 15% have the CD16A-VV allele.
When the researchers looked at progression-free survival by CD16A allele type, they found that people with the CD16A-FF and CD16A-FV alleles got more benefits from margetuximab. Progression-free survival for people with the CD16A-FF or CD16A-FV alleles was:
- 6.9 months for people treated with margetuximab and chemotherapy
- 5.1 months for people treated with Herceptin and chemotherapy
"This is the first prospective analysis of CD16A genotype as a predictor of efficacy from anti-HER2 therapy, and we demonstrated an enhanced [progression-free survival] benefit in patients carrying the … CD16A-F allele," Rugo said.
Margetuximab side effects
Like any cancer medicine, margetuximab can cause side effects, some of them severe.
The most common side effects of margetuximab reported in the SOPHIA study were:
- low red blood cell count
Rugo said the rates of overall side effects were similar in the two treatment groups and rates of severe side effects also were similar (14.8% for people treated with margetuximab and 17.4% for people treated with Herceptin).
"There were more infusion-related reactions with margetuximab compared to trastuzumab, of course in this population patients had already received multiple lines of trastuzumab therapy," Rugo said, but added that most were low-grade in nature, occurred with the first infusion, and were easily managed with premedication.
What this means for you
Margetuximab is not approved by the U.S. Food and Drug Administration (FDA), but MacroGenics, the company that makes margetuximab, said the medicine has been granted Fast Track designation by the FDA, which means the approval process will be expedited.
If you’ve been diagnosed with metastatic HER2-positive breast cancer that has grown after several lines of treatment, you may want to talk to your doctor about this study. If you’re willing to participate in a clinical trial, you may be able to be treated with margetuximab.
For more information on clinical trials, including a search tool specifically for metastatic breast cancer trials, visit the Breastcancer.org Clinical Trials pages.
Editor’s Note: On Dec. 16, 2020, the FDA approved Margenza (chemical name: margetuximab-cmkb) in combination with chemotherapy to treat people diagnosed with metastatic HER2-positive breast cancer who have been treated previously with two or more anti-HER2 regimens, at least one of which was for metastatic disease.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser
— Last updated on February 22, 2022, 9:58 PM
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