Giredestrant Halts Growth of Most Common Metastatic Breast Cancer
People with hormone receptor-positive HER2-negative metastatic breast cancer with an ESR1 mutation who took giredestrant and everolimus (brand name: Afinitor) lived longer without the cancer growing than people who took standard hormonal therapy and everolimus, according to a study.
Giredestrant is an experimental selective estrogen receptor downregulator (SERD), a type of hormonal therapy (also called endocrine therapy).
About 70% of people with metastatic breast cancer have hormone receptor-positive, HER2-negative disease.
Key takeaways
Among people diagnosed with cancer with an ESR1 mutation, progression-free survival was 10 months for people taking giredestrant and everolimus — 4.5 months longer than the control group. Progression-free survival is how long someone lives before the cancer grows.
Among all people in the study (people with cancers that did and didn’t have an ESR1 mutation), progression-free survival was 8.8 months for people on giredestrant and everolimus and 5.5 months for the control group.
Rates of side effects were similar between the two treatment groups; mouth sores and diarrhea were the most common.
What the results mean for you
If you’ve been diagnosed with metastatic hormone receptor-positive HER2-negative breast cancer that’s grown while you were taking a CDK4/6 inhibitor, you may want to ask your doctor if you might benefit from giredestrant once the medicine is approved.
Camizestrant (brand name: Etcamah) is another SERD used to treat metastatic hormone receptor-positive HER2-negative breast cancer with an ESR1 mutation that’s grown during CDK4/6 inhibitor treatment. No research has compared camizestrant and giredestrant head-to-head, so it’s unclear if one is better than the other. Other SERDs such as Orserdu (chemical name: elacestrant) and imlunestrant (brand name Inluriyo) are approved to treat cancers with ESR1 mutations that have grown during earlier treatment, but these two medicines haven’t been tested exclusively in patients who had already received a CDK4/6 inhibitor.
Why do the study?
If a hormone receptor-positive HER2-negative breast cancer develops an ESR1 mutation and grows while being treated with a CDK4/6 inhibitor and hormonal therapy, there’s no standard treatment. In some cases, a different CDK4/6 inhibitor might be recommended. In other cases, the hormonal therapy medicine might be switched — Faslodex (chemical name: fulvestrant) instead of an aromatase inhibitor.
Because giredestrant has been shown to be more effective than tamoxifen and the aromatase inhibitors in treating early-stage breast cancer, the researchers wanted to see if it could be a good treatment for metastatic disease.
About the study
The study included 373 women and men diagnosed with hormone receptor-positive HER2-negative metastatic breast cancer that grew or came back after treatment with a CDK4/6 inhibitor and hormonal therapy. Of these 373 people, 207 had cancer with an ESR1 mutation.
The people were split into two treatment groups:
183 took giredestrant and everolimus
190 took standard hormonal therapy (such as tamoxifen, an aromatase inhibitor, or Faslodex) plus everolimus. Most people in the study took the aromatase inhibitor exemestane (brand name: Aromasin) with everolimus.
Half the people were followed for longer than 19 months and half were followed for a shorter time.
Detailed results
The differences in progression-free survival — 10.5 months vs. 5.5 months for people with cancer with an ESR1 mutation and 8.5 months vs. 5.5 months for everyone in the study — were both statistically significant. This means the longer progression-free survival is likely due to the difference in treatment, rather than just because of chance.
Nearly all of the people taking giredestrant and everolimus (99%) had side effects. Similarly, about 97% of people receiving standard hormonal therapy and everolimus had side effects.
Serious side effects happened in 29% of people who took giredestrant plus everolimus compared with 23% of people who received standard hormonal therapy plus everolimus.
The researchers said that longer follow-up is needed to figure out if giredestrant helps people live longer (known as overall survival).
When will giredestrant be available?
The U.S. Food and Drug Administration (FDA) is currently reviewing two treatment applications for giredestrant to treat hormone receptor-positive HER2-negative breast cancer. The FDA is expected to review the application for early-stage breast cancer on Nov. 30 and the application for metastatic disease on Dec. 18.
Source
Mayer, E., et al. Giredestrant plus Everolimus in Advanced Breast Cancer. New England Journal of Medicine. Vol. 395, Issue 13, 1285-1298. Massachusetts Medical Society.