Breast cancer drug is effective for treatment-resistant uterine cancer

by Freda Kreier, Yale University

edited by Lisa Lock, reviewed by Andrew Zinin

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Uterine cancer is the deadliest cancer of the female reproductive system. Currently, clinicians treat the disease by using a mix of surgery and chemotherapy. But not everyone responds to this line of treatment, and those who fail first-line therapies are often left without next steps. Research by the Yale School of Medicine (YSM) shows that a breast cancer drug could provide new options for people suffering from treatment-resistant uterine cancer.

The new study, published May 14 in Clinical Cancer Research, suggests that doctors could use sacituzumab govitecan—a targeted chemotherapy approved by the U.S. Food and Drug Administration (FDA) and used to treat late-stage breast cancer—for these tough-to-crack cases. The drug helped shrink the size of uterine tumors in 28% of treatment-resistant patients, researchers found in the Phase II clinical trial, making it one of the most effective third-line treatments for uterine cancer to date.

While the drug still needs to be trialed with a larger number of patients, the results are promising, says lead author Alessandro Santin, MD, professor of obstetrics, gynecology, and reproductive sciences at YSM.

People with treatment-resistant uterine cancer have "very limited options," says Santin, who is also the clinical research team leader of gynecologic oncology at Yale Cancer Center. "That's why it's so important to develop new treatments."

Targeted chemotherapy for uterine cancer

About 3% of all women will develop uterine cancer in their lifetimes. The National Institutes of Health estimates that about 68,000 Americans will be diagnosed with uterine cancer in 2026. And while the majority will survive treatment, an estimated 14,400 will die of the disease.

That number is expected to rise. The number of uterine cancer cases is predicted to double by 2030—in part because, unlike colon cancer and breast cancer, uterine cancer is not included in standard screening.

Treatment options are also limited. However, researchers are now developing chemotherapy drugs that more specifically target tumor cells. These drugs, which often use antibodies to bind to specific proteins or other molecules on cancer cells, can help reduce some of the toxic effects of standard chemotherapy, which affects nearly all cells in the body.

More than a decade ago, Santin and his team identified a cell-surface protein—trophoblast cell surface antigen 2 (Trop-2)—that was highly expressed in uterine cancer cells. In theory, they could develop an antibody drug that targeted Trop-2 to deliver chemotherapy directly to uterine cancer cells, which could alleviate some of the worst side effects of chemotherapy.

The team developed this drug, called sacituzumab govitecan, in collaboration with the pharmaceutical company Immunomedics, now part of Gilead Sciences. In 2023, the FDA approved the use of sacituzumab govitecan for treatment-resistant breast cancer. Now, Santin and his colleagues wanted to know whether it would work for uterine cancer.

Drug is effective in treatment-resistant tumors

To test this, the researchers recruited a group of 50 patients with uterine cancer who had previously failed standard chemotherapy and surgery. Each patient received two doses of the drug every 21 days. After several rounds, the researchers measured tumor size.

Of the 50 patients recruited, 14 showed a 30% or greater reduction in tumor size. What's more, over 70% of patients saw tumor shrinkage overall.

This is significant, Santin says, because most chemotherapy treatments that are used at this stage in the disease have limited activity, with clinical response in less than 15% of patients. This suggests that sacituzumab govitecan may be more effective than standard chemotherapy.

The treatment did come with side effects. Many patients reported bone marrow and gastrointestinal issues, including reduced white blood count and diarrhea. Still, Santin says the side effects were manageable with supportive care and were overall less toxic than standard chemotherapy drugs.

The success of this study has laid the groundwork for a Phase III clinical trial to test the effectiveness of sacituzumab govitecan compared with standard chemotherapy in a larger group of patients. This trial is part of a larger trend toward targeted chemotherapies, Santin says, many of which may come onto the market in the next few decades.

"We are moving from a one-size-fits-all approach of chemotherapy to personalized treatment," he says. Drugs like sacituzumab govitecan that target a specific protein biomarker on cancer cells are "the future of oncology."

Publication details

Alessandro D. Santin et al, A Phase II Evaluation of the Efficacy and Safety of Sacituzumab Govitecan in Patients with Recurrent Uterine Cancer, Clinical Cancer Research (2026). DOI: 10.1158/1078-0432.ccr-26-0144

Journal information: Clinical Cancer Research

Key medical concepts

Cancer, Endometrialsacituzumab govitecanClinical Trials, Phase III as Topic

Clinical categories

OncologyObstetrics & gynecologyWomen's health Provided by Yale University Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

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