Elacestrant

Elacestrant (Orserdu) is a hormonal therapy used to treat hormone receptor-positive metastatic breast cancer. Elacestrant is part of a class of medicines called selective estrogen receptor degraders (SERDs). These medicines stop estrogen from fueling the growth of hormone receptor-positive breast cancer cells.

Elacestrant is the second medicine of this kind to be approved by the FDA. Imlunestrant (Inluriyo) is the third. Elacestrant and imlunestrant are available in pill form. The first approved SERD to treat breast cancer was fulvestrant (Faslodex), an injectable medicine.

How elacestrant works

Elacestrant is a hormonal therapy that was FDA approved in January 2023. It attaches to the estrogen receptors on hormone receptor-positive breast cancer cells, blocking estrogen's ability to attach to the cells and help them grow. As a selective estrogen receptor degrader, or SERD, elacestrant is also able to break down or weaken the estrogen receptor, making it inactive.

Elacestrant is the second SERD to be approved as a treatment for breast cancer. Fulvestrant was the first, approved in 2002. Elacestrant is a pill; fulvestrant is given by injection.

In one clinical trial, elacestrant was more effective than fulvestrant for some people with metastatic breast cancer. One reason for this could be that the oral formula can get higher levels of the drug into the body compared with fulvestrant injection.

Who gets elacestrant

Elacestrant can be used to treat advanced or metastatic hormone receptor-positive, HER2-negative breast cancer in women and men with breast cancer that:

• Has spread (progressed) while on another hormonal therapy, and 
• Tests positive for a mutation in the ESR1 gene

Elacestrant is available to people who have already tried another hormonal therapy, either an aromatase inhibitor or fulvestrant. For many people considering elacestrant, previous hormonal therapy was given with a CDK 4/6 inhibitor, a form of targeted therapy that blocks two growth-signaling proteins.

The combination of hormonal therapy with a CDK4/6 inhibitor is a standard first treatment for advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. It’s often effective at first but can eventually stop working. The cancer can become resistant to one or both treatments in this combination. This resistance may be due to changes in the ESR1 gene. Elacestrant offers a next treatment option if or when this occurs.

In the clinical trial that led to FDA approval for elacestrant, called the EMERALD trial, all participants had previously taken a CDK 4/6 inhibitor. On average, elacestrant worked for 3.8 months to control or treat the cancer in patients with an ESR1 mutation (compared with 1.9 months with fulvestrant). Researchers also found that the longer a person had taken a CDK 4/6 inhibitor, the greater effect elacestrant had on delaying cancer growth and spread.

Elacestrant was most effective for people who had previously taken a CDK 4/6 inhibitor for 12 or more months.

Elacestrant is more effective against breast cancers that test positive for an ESR1 mutation. ESR1 is a gene associated with estrogen response. Over time, the ESR1 gene can change or mutate. An ESR1 mutation develops in many advanced or metastatic breast cancers. The mutation can cause a tumor to become resistant to aromatase inhibitor hormonal therapy. In the past, when this occurred, fulvestrant would be given next.

When the FDA approved elacestrant, it also approved a test for the ESR1 mutation. The Guardant360 CDx assay is a blood test. The results are available in about 7 days. The test results will let you and your doctor know what gene mutations, such as ESR1, may be present in the cancer. This can help your doctor know if certain medicines, such as elacestrant, may be the right treatment for you.

If you are already on a treatment that is working, your doctor may advise continuing with it for now. ESR1 mutations develop over time. For this reason, ESR1 mutation testing is recommended for hormone receptor-positive cancers that continue to grow or spread after treatment with an aromatase inhibitor plus a CDK 4/6 inhibitor.

How elacestrant is given

Elacestrant is a pill that you take by mouth at the same time every day. It must be swallowed whole and taken with food. In contrast, the medicine fulvestrant is given by injection to the buttocks by a doctor or nurse every 2 weeks.

Elacestrant can be taken for as long as it continues to work and does not cause side effects that are harmful or too difficult to manage.

Side effects and things to remember

Most people taking elacestrant find the side effects manageable. Nausea is the most common side effect. In the clinical trial that led to the drug’s approval, most people who experienced nausea were able to manage it without anti-nausea medicine.

Besides nausea, other side effects can include:

• Constipation
• Decreased appetite
• Decreased red blood cell count (anemia)
• Decreased sodium level
• Diarrhea
• Headache
• Hot flashes, a common menopausal symptom
• Increased cholesterol or triglyceride level in the blood
• Worsened kidney or liver function tests
• Indigestion or heartburn
• Joint and muscle pain
• Stomach pain
• Tiredness
• Vomiting

While elacestrant is generally safe, there is a rare risk of increased fat (lipids) in the blood. Your doctor will test your blood before and while on elacestrant to watch for this.

Elacestrant can’t be given if you have liver problems.

Taking other medicines and supplements with elacestrant

Some medicines and supplements should not be taken along with elacestrant.

Medicines that can slow down how quickly the body processes elacestrant

Some medicines slow the body’s processing of elacestrant, increasing the risk of side effects:

• Antifungal medicines used to treat fungal infections, such as:
  • Fluconazole (Diflucan)
  • Itraconazole (Sporanox, Onmel, Tolsura)
  • Ketoconazole (Nizoral)
  • Voriconazole (Vfend)
• Antibiotics, such as:
  • Ciprofloxacin (Cipro, Proquin)
  • Clarithromycin (Bioxin)
  • Erythromycin (Ery-Tab)
• Calcium channel blockers, such as:
  • Diltiazem (Cardizem and other brand names)
  • Verapamil (Verelan, Calan, Covera, Isoptin)
• The antidepressant Nefazodone (Serzone)

In addition, grapefruit and grapefruit juice can slow the breakdown of elacestrant.

Medicines that speed up the body’s processing of elacestrant

Some medicines and supplements cause the body to process elacestrant too quickly. This lowers the amount of elacestrant in the body and makes it less effective. These include:

• Seizure medicines used to treat epilepsy or other seizure disorders, bipolar disorder, or nerve pain:
  • Carbamazepine (Tegretol)
  • Cenobamate (Xcopri)
  •  Phenobarbital
  • Phenytoin (Dilantin)
• Rifampin (Rifadin, Rimactane), an antibiotic used to treat tuberculosis and other infections
• St. John’s wort, an herbal supplement some people use help with depression and mood

Be sure to share a list of anything you're taking with your healthcare team. They may advise stopping a certain medicine or supplement, changing the dose, or monitoring you more closely while you’re taking elacestrant.

Other medicines that can interact with elacestrant

Taking elacestrant can increase the risk of side effects from medicines taken for other health conditions. It does this by increasing the levels of those medicines in the body. Examples include:

• Medicines for HIV (Human Immunodeficiency Virus)
  • Cobicistat (Tybost)
  •  Efavirenz
  •  Etravirine
  • Nelfinavir (Viracept)
  • Ritonavir (Norvir)
• Digoxin (Lanoxin), used to treat heart failure, irregular heart rhythm, and other heart conditions
• Certain statins, such as rosuvastatin (Crestor) and atorvastatin (Lipitor, Atorvaliq), used to low cholesterol and triglycerides (a type of fat) in the blood

Financial assistance for elacestrant

If you’re considering elacestrant, reach out to your health insurance company to find out if the drug is covered, how long it may be covered, and what the out-of-pocket cost will be for you. If cost is a challenge, Stemline Therapeutics, the company that makes elacestrant, might be able to help.

Through their patient support program, Stemline provides information and resources to help eligible individuals get started on treatment. They also offer a rapid start program for people who are awaiting insurance approval.

For information on patient support services or financial assistance programs, call 1-833-478-3654 (833-4-STEMLINE) or visit Stemline ARC.