Study: Trodelvy benefits people with advanced hormone-positive metastatic breast cancer
The study TROPiCS-2 showed that the drug Trodelvy (sacituzumab govitecan) improved progression-free survival when compared to chemotherapy in people with advanced metastatic ER/PR-positive, HER2-negative breast cancer who have few other treatment options. This drug does not yet have FDA approval for use in the hormone-positive setting. (Posted 1/18/23)
Update: On 02/03/2023 the FDA approved Trodelvy for patients with locally advanced or metastatic breast cancer who have received hormonal therapy and at least two other types of treatment in the metastatic setting.
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Most relevant for: People with ER/PR-positive, HER2-negative metastatic breast cancer. It may also be relevant for:
- people with metastatic or advanced cancer
- people with ER/PR + cancer
Strength of Science: High
Research Timeline: Post Approval
What is this study about?
The study, called TROPiCS-02, is a large clinical trial comparing the drug Trodelvy (sacituzumab govitecan) to chemotherapy in people with HR-positive, breast cancer.
Trodelvy is a type of treatment known as an antibody-drug conjugate (ADC). These drugs are also referred to as “smart drugs.” You can read more about Trodelvy here.
Smart drugs combine two molecules. Trodelvy is a combination of a chemotherapy drug and an antibody that delivers it directly to cancer cells. The chemotherapy drug then kills the cancer cells, while sparing normal cells.
Trodelvy binds to a protein on cancer cells called Trop-2. The Trop-2 protein is present on almost all , and cells.
Why is this study important?
HR-positive, breast cancer is often treated with hormone therapy combined with other treatments such as targeted therapies. While this treatment approach has been shown to improve survival, these cancers eventually become resistant to hormone therapy. Chemotherapy is then usually given, although outcomes are poor due to low response rates and side effects from treatment. Trodelvy had already received approval for people with TNBC (read more here). Based on the results of this study, in February, 2023 the approved Troveldy for treating people with , metastatic breast cancer.
All participants had advanced , metastatic breast cancer and had previously received treatment. Almost all participants had already been treated with a CDK4/6 inhibitor (a type of used for hormone-positive breast cancer) and had three lines of chemotherapy.
Participants were randomly assigned to receive Trodelvy (272) or chemotherapy (271).
- Participants who received Trodelvy had no cancer growth for 1.5 months longer than those who received chemotherapy (5.5 months compared to 4.0 months).
- Participants who received Trodelvy survived just over 3 months longer than those who received chemotherapy (14.4 months compared to 11.2 months).
Trodelvy and status
HER2 is a protein on the surface of all breast cells. High levels of can cause cells to grow and divide uncontrollably.
All breast cancers are tested for . scores range from 0 to 3+ (3 or higher). In the past, a tumor with a score of 0 to 1+ was called HER2-negative; a score of 2+ was considered borderline, while a score of 3+ was considered . Now, however, a score of 1+ or 2+ is considered to be HER2-low.
When researchers looked closely at status in this study, they found that participants with HER2-low breast cancer who received Trodelvy had no cancer growth for 2.2 months longer than those participants with HER2-low breast cancer who received chemotherapy (6.4 months compared to 4.2 months).
Trodelvy and Trop-2 status
Trop-2 is a protein on the surface of some breast cancer cells. Unlike , Trop-2 levels may range from very low to very high. Similar to , Trop2 can cause these cells to grow and divide quickly. Trodelvy works by binding to the Trop-2 protein and delivering a drug that kills the cancer cell.
Researchers found that Trodelvy benefited patients regardless of how much or how little Trop-2 protein was present. This suggests that Trop-2 testing is not required for treatment with Trodelvy.
As with most cancer medicines, Trodelvy may cause side effects. The most common side effects from Trodelvy include:
- neutropenia (abnormally low levels of white blood cells)
- hair loss
- decreased appetite
- abdominal pain
The FDA-required labeling for Trodelvy warns about the possibility of severe neutropenia or diarrhea.
- TROPiCS-02 was a large study that took place in 113 locations in the United States, Canada and Europe.
- Few participants chose to stop treatment in the Trodelvy group, which improves confidence in the results.
- Some participants (8%) randomly assigned to the chemotherapy group were not treated, likely because the participant chose not to receive chemotherapy.
- Most participants (95%) had visceral metastases (metastases to soft internal organs such as the lungs). Because having visceral metastases is linked to shorter progression-free survival and a higher risk for neutropenia, this could have impacted the study results.
- The differences in prior treatments among participants and the physician’s choice of chemotherapy may have affected the study findings.
Results from two prior studies—IMMU-132 and ASCENT—showed that people with triple-negative breast cancer benefited from Trodelvy. Now, as shown by the TROPiCS-02 study, Trodelvy may also benefit those with advanced , metastatic breast cancer.
What does this mean for me?
If you have been diagnosed with advanced or HER2-low breast cancer and your treatment options are limited, you may want to talk to your doctor about Trodelvy.
Based on this study, NCCN guidelines have been updated to include Trodelvy as a treatment option for people with advanced , breast cancer who have received prior treatment, including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane).
Rugo HS, Bardia A, Marmé F, et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer. Journal of Clinical Oncology; 10;40(29):3365-3376. Published online August 26, 2022.
Schmid P, Cortes J, Marmé F, et al. Sacituzumab govitecan efficacy in HER+/HER2– breast cancer by immunohistochemistry status in the phase 3 TROPiCS-02 study. ESMO Congress 2022. Abstract 214MO. Presented September 10, 2022.
Rugo H, Bardia A, Marmé, F, et al. GS1-11 Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC): Efficacy by Trop-2 Expression in the TROPiCS-02 Study of Patients (Pts) With HR+/HER2– Breast Cancer (mBC). San Antonio Breast Cancer Symposium 2022. Abstract GS1-11. Presented December 6,2022.
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.
Share your thoughts on this XRAY review by taking our brief survey.
- Is Trodelvy a treatment option for my type of breast cancer?
- If Trodelvy is not an option for me now, might it be an option in the future?
- What side effects might I experience with this treatment?
- If I have serious side effects, will I need to stop treatment?
- Are any other agents available to treat my cancer?
The following studies look at treatment for people with ER-positive breast cancer.
- Studies for People With ER-Positive, Advanced or Breast Cancer (VERITAC Studies): The VERITAC studies are looking at the safety of an oral study medicine, ARV-471 (also known as vepdegestrant or PF-07850327), and how well it works either alone or combined with another breast cancer medicine, palbociclib (also known as IBRANCE®).
- Treatment Studies for People with ER-Positive, Advanced or Breast Cancer (TACTIVE-U): The TACTIVE-U studies are looking at the safety of an oral study medicine, ARV-471 (also known as vepdegestrant), and how well it works when combined with other breast cancer medicines.
- NCT04673448: Combining the Dostarlimab and Niraparib for Advanced or Breast, Ovarian or Pancreatic Cancer with an Inherited or Tumor Mutation. This study is looking at the effectiveness of combining the , and the dostarlimab for treating people with an inherited mutation (found with genetic testing) or a tumor mutation (found through tumor testing) who have advanced breast, pancreatic or ovarian cancer.
- NCT05501886: Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or HR+/HER2- Breast Cancer (VIKTORIA-1). This study is looking at the efficacy and safety of the selective receptor degrader (SERD) gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.
- NCT04975308: A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3). This study will evaluate the efficacy and safety of the selective receptor degrader (SERD) imlunestrant, how it works compared to standard hormone therapy, and how well imlunestrant with abemaciclib works compared to imlunestrant in participants with breast cancer that is ER-positive and .
- NCT05306340: A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With Exemestane Plus Everolimus in Participants With Receptor-Positive, , Locally Advanced or Breast Cancer (evERA Breast Cancer). This study will evaluate the efficacy and safety of the selective receptor degrader (SERD) giredestrant, plus everolimus compared with exemestane plus everolimus in people with receptor ER-positive, locally advanced or breast cancer who have had previous treatment with a CDK4/6 inhibitor and hormone therapy.
- NCT03344965: Expanded - Treating Breast Cancer in People without gBRCA Mutations. This study will look at whether is also effective for treating breast cancer in people who do not have an inherited mutation. The study is enrolling people with an in or an acquired (tumor) mutation in or .
- NCT03685331: , Palbociclib and Fulvestrant for BRCA-Associated, ER/PR+/HER2-Negative Breast Cancer. This study is looking at the side effects and best dose of palbociclib when given with and fulvestrant for people with HR+/HER2-negative mBC who have a or mutation.
- NCT04072952: ARV-471 Alone and in Combination With Palbociclib in Patients With ER+/HER2- Locally Advanced or Breast Cancer. This is a dose escalation and expansion study to learn the safety and tolerability of ARV-471 alone and combined with palbociclib in people with ER+/HER2- locally advanced or breast cancer who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.
- NCT04448886: Sacituzumab Govitecan +/- Pembrolizumab In HR+ / - MBC. This research study is evaluating the safety and effectiveness of Sacituzumab Govitecan with or without Pembrolizumab in HR+/HER2- breast cancer.
- NCT04563507: Combined Immunotherapies in ER+ Breast Cancer. Patients receiving standard therapy for HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each lesion.
- NCT04895358: Pembrolizumab Plus Chemotherapy Versus Plus Chemotherapy for HR+/HER2- Inoperable or Breast Cancer (KEYNOTE-B49). The study will look at the safety and efficacy of pembrolizumab plus chemotherapy compared to chemotherapy alone in the treatment of HR+/HER2- locally recurrent inoperable or breast cancer.
Other clinical trials for people with breast cancer can be found here.
The following organizations offer peer support services for people with, or at high risk for breast cancer:
- FORCE peer support:
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Connect online with our Private Facebook Group.
- Join our virtual and in-person support meetings.
- Other organizations that offer breast cancer support:
The National Comprehensive Cancer Network (NCCN) guidelines for the treatment of advanced or ER-positive breast cancer include the following:
- 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 () 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).
- The NCCN lists as the preferred treatment combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + with a CDK4/6 inhibitor:
- 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 () 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)
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