Study: New oral drug treatment for some advanced breast cancer

Relevance: High

Strength of Science: High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

A research study (called the EMERALD study) looked at how well people with metastatic breast cancer did when treated with a new drug called Oserdu (elacestrant). 

The study looked at people with breast cancer that:

• was metastatic
• was HR-positive
• was HER2-negative
• came back or got worse after standard treatment

People in the study had received up to two types of treatment before joining the study. Study participants were separated into 2 groups:

• half of the people receive Oserdu
• half received standard hormone therapy

Researchers compared how well people in the Oserdu group did compared to people in the standard hormone therapy group. 

During the EMERALD study, a blood test was used to look for a marker found in the cancer known as an ESR1 mutation. ESR1 mutations are made by breast cancers that no longer respond to treatment with a type of hormone therapy known as an aromatase inhibitor (AI).

• half of the participants had a mutation in ERS1.

What type of treatment is Oserdu?

Oserdu is a type of hormone therapy drug called a selective estrogen receptor degrader (SERD). 

Why is this study important?

People with HR-positive, HER2-negative, metastatic breast cancer that comes back or gets worse after treatment have few additional treatment options.

Study findings

The EMERALD study findings included:

• people who received Orserdu had a longer time until cancer came back or became worse (progression free survival) than people who did not receive Oserdu
• among people with an ESR1 mutation, those who received Orserdu had a longer time until cancer came back or became worse than people who did not receive Oserdu
• early results suggest that Orserdu may also increase how long people lived (overall survival) compared to the standard of care but the final overall survival results are not yet available

Side effects

Side effects occurred in most participants, regardless of treatment type. The most common side effects while taking Orserdu included nausea, fatigue, decreased appetite and joint pain.

FDA approval

Based on the results of EMERALD, the FDA has approved Orserdu to treat advanced HR-positive, HER2-negative breast cancer. The FDA has also approved a blood test called Guardant360, which tests for tumor mutations in the ESR1 gene. People with an ESR1 tumor mutation benefit most from treatment with Orserdu.

What does this mean for me?

If you have HR-positive, HER2-negative metastatic breast cancer that has come back or worsened after treatment with hormone therapy and a CDK4/6 inhibitor, you may benefit from the drug Orserdu.  

Orserdu improved progression-free survival and may also improve overall survival, particularly for people who have an ESR1 tumor mutation.

Reference

Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256.

Kaklamani V, Bidard FC, Neven P, et al: EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2– metastatic breast cancer: Updated results by duration of prior CDK4/6 inhibitor in metastatic setting. 2022 San Antonio Breast Cancer Symposium. Abstract GS3-01. Presented December 8, 2022.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 3/20/23

Study findings

The EMERALD trial was a worldwide large study that looked at how well the drug Orserdu worked to treat people with advanced, HR-positive breast cancer that worsened after first- or second-line treatment with hormone therapy and a CDK4/6 inhibitor. All participants received a CDK4/6 inhibitor and hormone therapy for up to 18 months before being assigned to Orserdu or hormone therapy treatment.

Outcomes from all participants

• 239 participants were randomly chosen to receive Orserdu; 238 participants received standard hormone therapy.
  • Participants had longer intervals of progression-free survival with Orserdu than they did with hormone therapy.
  • Longer pretreatment with a CDK4/6 inhibitor and hormone therapy benefited both groups of participants.

            Progression-free survival among all participants

Outcomes among participants with ESR1 tumor mutations

• Participants also had a blood test to screen for tumor mutations in the ERS1 gene.  About half of the participants (228) had a mutation in ERS1.
• Among participants with ESR1 tumor mutations who were pre-treated for at least 12 months, the cancers of those who received hormone therapy worsened about 2 months later, while those who received Orserdu experienced worsened cancer about 9 months later.

            Progression-free survival among participants with an ESR1 mutation

These early results suggest that Orserdu may increase overall survival compared to the standard of care but the final overall survival results are not yet available.

Side effects

Side effects occurred in most participants, regardless of treatment type. The most common side effects while taking Orserdu included nausea, fatigue, decreased appetite and joint pain.

Strengths and limitations

Strengths

• This study required that all participants had already received treatment with a CDK4/6 inhibitor and hormone therapy, which is what current guidelines recommend.

Limitations

• Most participants were white. It is not known whether other racial or ethnic groups would benefit the same from treatment with Orserdu.
• While men were allowed to participate in the trial, almost all participants were female (one man participated). It is not known whether men would benefit the same from treatment with Orserdu.

Context

Almost 20 years have passed since the SERD fulvestrant was approved to treat people with HR-positive metastatic breast cancer.

Orserdu is the first oral SERD to show improved progression-free survival compared with the standard of care for people with advanced breast cancer. Orserdu is an oral medication, which makes it easier to take than fulvestrant, which is given as an injection.