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Study: New oral drug treatment for some advanced breast cancer

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Contents

Study findings Guidelines
Strengths and limitations Clinical trials
What does this mean for me? Related resources
Questions for your doctor Get support

STUDY AT A GLANCE

What is this study about?

This study looked at a new drug called Oserdu (elacestrant) used to treat , metastatic breast cancer. Oserdu is a type of hormone therapy drug called a selective estrogen receptor degrader (SERD). Researchers looked at how well this new SERD worked to treat people with advanced breast cancer whose cancer worsened after standard treatment.

Why is this study important?

People whose , breast cancer worsens after treatment have few subsequent treatment options. The EMERALD research study showed that a new SERD called Orserdu (elacestrant) significantly increased progression-free survival, the time until cancer came back or became worse, in people who had received up to two types of prior treatment. 

During the Emerald study, a blood test was used to look for a tumor marker known as ESR1. The ESR1 marker is found in cancers that no longer respond to treatment with a type of hormone therapy known as an aromatase inhibitor (AI).

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

Study findings

The EMERALD trial was a worldwide large study that looked at how well the drug Orserdu worked to treat people with advanced, 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

*Orserdu = 6, 12 or 18 months on a CDK4/6 inhibitor and hormone therapy, then Orserdu among all participants (i.e., with or without an ESR1 mutation).

**Hormone therapy = 12 or 18 months on a CDK4/6 inhibitor and hormone therapy, then more hormone therapy among all participants (i.e., with or without an ESR1 mutation).

 

Pretreatment time on CDK 4/6 inhibitor
plus hormone therapy

 

6 months
pre-treatment

12 months
pre-treatment

18 months
pre-treatment

Orserdu* 2.8 months 3.8 months 25.5 months
Hormone therapy** 1.9 months 1.9 months 3.3 months

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

*Orserdu = 0-18 months, 12 or 18 months on a CDK4/6 inhibitor and hormone therapy, then Orserdu among participants with an ESR1 mutation.

**Hormone therapy = 12 or 18 months on a CDK4/6 inhibitor and hormone therapy, then more hormone therapy among participants (with an ESR1 mutation).

 

Pretreatment time on
CDK 4/6 inhibitor plus hormone therapy

 

6 months
pre-treatment

12 months
pre-treatment

18 months
pre-treatment

Orserdu* 4.1 months 8.6 months 8.6 months
Hormone therapy** 1.9 months 1.9 months 2.1 months

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.

Side effect Orserdu Hormone therapy
Any 92% 86%
Nausea 35% 19%
Fatigue 19% 19%
Decreased appetite 15% 9%
Joint pain 14% 16%


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 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.

What does this mean for me?

If you have , metastatic breast cancer that has come back or worsened after treatment with hormone therapy and a CDK4/6 inhibitor, you may benefit from the SERD 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 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– breast cancer: Updated results by duration of prior CDK4/6 inhibitor in 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

This article is relevant for:

People with HR-positive, HER2-negative advanced breast cancer

This article is also relevant for:

People with breast cancer

People with metastatic or advanced cancer

People with ER/PR + cancer

Be part of XRAY:

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network (NCCN) brings together national expert panels that create guidelines for cancer treatment. NCCN guidelines for the treatment of advanced or ER-positive breast cancer include the following:

Genetic testing

  • All people diagnosed with breast cancer meet guidelines for genetic counseling and testing. 

NCCN preferred treatment options

The NCCN lists the following as preferred treatments for ER-positive and breast cancer:

  • for people with or mutations:
    • The NCCN lists Lynparza (olaparib) or () for people with an inherited or mutation. 
  • First line therapy
    • The NCCN lists as the preferred treatment combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + with a CDK4/6 inhibitor:
      •  abemaciclib (Verzenio), palbocicib (Ibrance) or ribociclib (Kisqali). 
  • For second, third or later lines of therapy, the NCCN lists the following targeted therapies or combinations treatments:
    • a combination of hormonal therapy (aromatase inhibitor or Fulvestrant) plus with a CDK4/6 inhibitor for people who have not previously received a CDK4/6 inhibitor
    • Enhertu (trastuzumab deruxtecan) for people whose tumors are HER2-low ( 1+ or 2+), who received chemotherapy in the setting and their cancer no longer responds to hormonal therapy 
    • Piqray (apelisib) for cancers that test positive for a PIK3CA-mutation
    • Oserdu (elacestrant) for , cancers that test positive for an ESR1 mutation
    • Lynparza (olaparib) or () for BRCA1/BRCA2 for tumors with or mutation
    • a combination of everolimus and hormonal therapy
    • hormonal therapy alone
    • Trodelvy (sacituzumab govitecan-hziy) for , cancers after prior treatment including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane)

Updated: 03/21/2023

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Should I have the to see if I have an ESR1 mutation?
  • Would I benefit from treatment with Orserdu?
  • Do I have other treatment options?

Open Clinical Trials
Open Clinical Trials

The following studies look at treatment for people with ER-positive breast cancer.  

Other clinical trials for people with breast cancer can be found here.

Updated: 03/09/2023

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 11/29/2022

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