Study: Trodelvy benefits people with advanced hormone-positive metastatic breast cancer

Relevance: Medium-High

Strength of Science: High

Research Timeline: Post Approval

Relevance Rating Details

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 metastatic HR-positive, HER2-negative 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 HR-positive, HER2-negative and triple-negative breast cancer cells.

Why is this study important?

Metastatic HR-positive, HER2-negative 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 FDA approval for people with metastatic TNBC (read more here). Based on the results of this study, in February, 2023 the FDA approved Troveldy for treating people with HR-positive, HER2-negative metastatic breast cancer.

Study findings

All participants had advanced ER/PR-positive, HER2-negative metastatic breast cancer and had previously received treatment. Almost all participants had already been treated with a CDK4/6 inhibitor (a type of targeted therapy 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 HER2 status
HER2 is a protein on the surface of all breast cells. High levels of HER2 can cause cells to grow and divide uncontrollably.

All breast cancers are tested for HER2. HER2 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 HER2-positive. Now, however, a score of 1+ or 2+ is considered to be HER2-low.

When researchers looked closely at HER2 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 HER2, Trop-2 levels may range from very low to very high. Similar to HER2, 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.

Side effects
As with most cancer medicines, Trodelvy may cause side effects. The most common side effects from Trodelvy include:

• nausea
• neutropenia (abnormally low levels of white blood cells)
• diarrhea
• fatigue
• anemia
• vomiting
• hair loss
• constipation
• decreased appetite
• rash
• abdominal pain

The FDA-required labeling for Trodelvy warns about the possibility of severe neutropenia or diarrhea.

Strengths and limitations

Strengths

• TROPiCS-02 was a large randomized 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.

Limitations

• 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.

Conclusions

Results from two prior studies—IMMU-132 and ASCENT—showed that people with triple-negative metastatic breast cancer benefited from Trodelvy. Now, as shown by the TROPiCS-02 study, Trodelvy may also benefit those with advanced ER/PR-positive, HER2-negative metastatic breast cancer.

What does this mean for me?

If you have been diagnosed with advanced HER2-negative 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 HR-positive, HER2-negative breast cancer who have received prior treatment, including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane). 

Reference

Rugo HS, Bardia A, Marmé F, et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic 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– metastatic breast cancer by HER2 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– Metastatic 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.

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posted 1/18/23