A new hormonal therapy is now available for people with treatment-resistant advanced or metastatic breast cancer.
The U.S. Food and Drug Administration (FDA) approved the Stemline Therapeutics drug Orserdu (elacestrant) on January 27 for post-menopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who had undergone at least one line of endocrine therapy, according to an FDA press release. The drug was approved under the FDA Fast Track process, designed to “facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.”
The agency also approved the Guardant360 CDx assay test as a companion diagnostic device to identify patients with breast cancer who may benefit from treatment with Orserdu.
“This is the first endocrine therapy approved since 2002 and the only one approved specifically for patients with tumors that had mutations in the estrogen mutation gene,” says Virginia Kaklamani, MD, DSc, a professor of medicine and the Ruth McLean Bowman Bowers Chair in Breast Cancer Research and Treatment at MD Anderson Cancer Center at UT Health San Antonio in Texas.
Dr. Kaklamani was a member of the steering committee for Orserdu’s trials and one of the principal investigators. “This approval gives an oral therapy option with only low-grade toxicities to women with metastatic breast cancer,” she says.
Tumors With ESR1 Mutations Can Often Be More Aggressive and Hard to Treat
Orserdu (elacestrant) is a new type of hormonal treatment for advanced breast cancer, says Halle Moore, MD, the director of breast medical oncology in the department of hematology and oncology at Cleveland Clinic in Ohio.
“Over time, most metastatic breast cancers treated with hormonal agents will develop resistance to treatment. One mechanism of resistance is mutations in ESR1,” says Dr. Moore, who was not involved in the trials for Orserdu.
These mutations cause the estrogen receptor to be activated all the time, whether or not estrogen is present, says Daniel Stover, MD, a breast medical oncologist with the Ohio State University Comprehensive Cancer Center at the Richard J. Solove Research Institute in Columbus. Dr. Stover was also not involved in the clinical trials for Orserdu.
Tumors with ESR1 mutations tend to be more aggressive and resistant to some standard anti-estrogen therapies, like aromatase inhibitors such as letrozole or anastrozole, says Stover.
ESR1 mutations are present in an estimated 20 to 40 percent of ER-positive, HER2-negative advanced or metastatic breast cancer, according to a paper published in the August 2021 issue of the BMC journal Breast Cancer Research.
“ESR1 mutations can be detected either through tissue biopsies or through ‘liquid biopsy’ blood-based tests. This means we will likely do more testing to look for this and other cancer mutations,” says Stover.
Orserdu Delayed Cancer Progression Longer Than Standard-of-Care Drugs
The approval was based on the phase 3 trial EMERALD, a randomized, open-label, active-controlled, multicenter trial of 478 post-menopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer; 228 of the subjects had ESR1 mutations.
Participants were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor. Eligible patients could have received up to one prior line of chemotherapy in the advanced or metastatic setting.
The subjects were randomly placed 1:1 into two groups: one that received Orserdu, and one that received the researchers’ choice of endocrine therapy (considered standard of care), which included fulvestrant or an aromatase inhibitor.
Investigators found that Orserdu reduced the risk of disease progression or death by 45 percent versus standard-of-care endocrine therapies in patients whose tumors had ESR1 mutations.
The median progression-free survival was 8.6 months on Orserdu, versus 1.9 months for standard of care, in patients who had been treated with a CDK4/6 inhibitor for at least 12 months.
“This trial demonstrated that elacestrant showed significantly longer time before progression relative to standard of care therapy, particularly in those patients whose tumors harbor an ESR1 mutation,” says Stover. This is a good thing for patients who fit these features, says Stover. “Orserdu offers a new oral, well-tolerated therapy to our tool kit of treating metastatic breast cancer,” he says.
Moore agrees, saying, “This is an important new option for many of our patients and may allow a delay in the time before a patient requires chemotherapy for treatment of their cancer.”
Orserdu Appears to Be Safe and Has Only Mild Side Effects
The recommended elacestrant dose is 345 mg taken orally with food once daily until disease progression occurs or the drug is no longer tolerated, according to the prescribing information.
For the most part, drug trials showed that side effects were mild and included nausea, musculoskeletal pains, fatigue, headache, and liver enzyme elevation, says Moore. “A higher rate of elevated blood lipids was observed with Orserdu and monitoring of lipid profile is recommended,” she says, but “the medication appears to be very safe.”
Cost and Insurance Coverage for Orserdu
Orserdu will soon be available in the United States, says Elcin Barker Ergun, the CEO of the Menarini Group, which owns Stemline Therapeutics.
“Stemline is committed to helping patients access Orserdu and will be offering services to overcome access barriers,” she says. This includes ARC, a patient support program that is available to help guide eligible patients through the various aspects of starting treatment, including providing educational information to help them understand their insurance coverage and identify potential financial assistance options, says Ergun.
For more information, patients and healthcare professionals can call 833-4-STEMLINE (833-478-3654).
The wholesale acquisition cost (WAC) for Orserdu was $21,369 for a 30-day supply of 345 mg tablets, says Ergun. Actual cost to the patient will depend on insurance coverage.
Modern Treatment Options Mean Women With Metastatic Breast Cancer Are Living Longer
Metastatic breast cancer (also called stage 4) is when breast cancer spreads beyond the breast and nearby lymph nodes to the bones, liver, brain, or another organ. It’s estimated that more than 168,000 women in the U.S. have metastatic breast cancer (men can get metastatic breast cancer, too), according to Susan G. Komen, a nonprofit breast cancer advocacy group.
Thanks to research breakthroughs and modern treatments, on average, people with metastatic breast cancer are living longer than ever. About one in three women diagnosed with metastatic breast cancer in the United States live at least five years after diagnosis, and some women may live 10 or more years beyond diagnosis, according to the organization.