FDA Approval: Sacituzumab govitecan (Trodelvy) for Breast Cancer

A guided missile, more or less

Sacituzumab govitecan is sold as Trodelvy. It is an antibody-drug conjugate. That name describes the design: an antibody joined by a chemical linker to a cell-killing drug.

The antibody half looks for Trop-2, a protein carried on the surface of many breast cancer cells. The drug half is SN-38, a topoisomerase I inhibitor. Topoisomerase I is an enzyme that nicks DNA so it can unwind. SN-38 blocks the repair of those nicks, and the damage kills the cell.

The label describes the sequence. The antibody binds Trop-2, the cell pulls the whole package inside, and the linker breaks to release SN-38 there. The idea is to bring a harsh drug to the cells that carry the target.

FDA first approved Trodelvy in April 2020. The label has grown several times since.

Who the label covers now

There are three groups, and they are not interchangeable.

For triple-negative breast cancer, first line, Trodelvy is approved on its own for adults with unresectable locally advanced or metastatic disease who are not candidates for PD-1 or PD-L1 inhibitor treatment. It is also approved with pembrolizumab for some tumors. Those tumors must express PD-L1 at a combined positive score of 10 or more. An FDA-authorized test measures that score.

For triple-negative breast cancer, second line or later, it is approved for adults who have had two or more prior systemic therapies, at least one of them for metastatic disease.

The third group is hormone receptor-positive, HER2-negative disease. Here it is approved for adults who have had endocrine-based treatment. They must also have had at least two more systemic therapies for metastatic disease.

Triple-negative means the tumor lacks estrogen receptors, progesterone receptors, and extra HER2. Those are the three targets that most breast cancer drugs aim at. Our page on breast cancer explains how receptor status is worked out.

What the trials showed

ASCENT enrolled 529 people with previously treated metastatic triple-negative disease. Trodelvy was compared with a single chemotherapy of the doctor's choice. Median progression-free survival was 4.8 months against 1.7 months, with a hazard ratio of 0.43. Median overall survival was 11.8 months against 6.9 months, with a hazard ratio of 0.51.

TROPiCS-02 enrolled 543 people with hormone receptor-positive, HER2-negative disease. All had grown worse after a CDK 4/6 inhibitor, endocrine therapy, and a taxane. Median progression-free survival was 5.5 months against 4 months. Median overall survival was 14.4 months against 11.2 months, with a hazard ratio of 0.789.

ASCENT-03 enrolled 558 people with untreated advanced triple-negative disease who were not candidates for a PD-1 or PD-L1 drug. Median progression-free survival was 9.7 months against 6.9 months. Response rates were 50 percent and 47 percent. Overall survival data were not yet mature.

ASCENT-04 enrolled 443 people whose tumors expressed PD-L1 at a score of 10 or more. Trodelvy with pembrolizumab was compared with chemotherapy plus pembrolizumab. Response rates were 61 percent and 55 percent. Our page on immunotherapy explains what pembrolizumab does.

Overall survival counts deaths. Progression-free survival counts scan findings, and a gain there does not always turn into a longer life.

The boxed warning, and why it is there

The label carries a boxed warning for neutropenia and diarrhea. That is FDA's strongest warning format.

Neutropenia means a low count of neutrophils, the white cells that fight bacteria. The label says it can be severe, life-threatening, or fatal. Treatment is withheld if the absolute neutrophil count falls below 1500 per cubic millimeter. It is also withheld if fever develops while counts are low. Blood counts are checked through treatment. A growth factor called G-CSF is given up front to people at higher risk.

Diarrhea can also be severe. The label directs doctors to check for infection first. If none is found, they start loperamide. Fluid and salts are given as needed.

Nausea occurred in 63 percent of people and vomiting in 33 percent, so medicines to prevent both are given before each dose. Infusion reactions are monitored during the drip and for at least 30 minutes afterward.

One genetic detail matters here. People who carry two copies of a variant called UGT1A1*28 clear SN-38 more slowly. The label says they face a higher risk of low white cell counts. They also face more fever during low counts, and more low red cell counts.

When to call the team during treatment

These are the label's own triggers, not general advice. Anyone on this drug should report:

• A fever, especially any temperature reading their team has told them to treat as a fever
• Diarrhea that is new, frequent, or not settling
• Nausea or vomiting that stops normal eating and drinking
• Shortness of breath, flushing, or rash during or soon after an infusion

Fever while neutrophil counts are low is a medical emergency and needs same-day assessment.

The population picture

SEER data help place these numbers. Triple-negative disease, listed as HR-negative and HER2-negative, is about 11 percent of female breast cancers. Its five-year relative survival is 78.7 percent across all stages. Once the cancer is distant, that figure is 14.9 percent.

Hormone receptor-positive, HER2-negative disease is about 70 percent of cases. Its five-year relative survival is 95.8 percent overall, and 38.1 percent for distant disease.

Those distant-stage figures are the setting Trodelvy is used in. They cover thousands of people diagnosed between 2016 and 2022. Each was treated with what was on hand then. They describe a group and cannot describe a reader.

What this approval cannot tell you

An approval sets out who is eligible in general terms. Whether it fits one person is a separate question. Receptor status, PD-L1 testing, earlier treatments, liver function, blood counts, and a person's own goals all feed into it.

The gains reported are real but measured in months of median time, and a median has people on both sides of it. Neither trial reported a cure.

The first-line triple-negative indications rest partly on progression-free survival, with overall survival still immature in ASCENT-03. That answer is not in yet.

Sources

• DailyMed, TRODELVY (sacituzumab govitecan-hziy) prescribing information — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57a597d2-03f0-472e-b148-016d7169169d
• FDA, FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer
• FDA, FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer — https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line
• NCI, Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer — https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-sacituzumab-govitecan-triple-negative-breast-cancer
• SEER Cancer Stat Facts, Female Breast Cancer Subtypes — https://seer.cancer.gov/statfacts/html/breast-subtypes.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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