Breast Cancer Drug Is Effective for Treatment-Resistant Uterine Cancer

A breast cancer drug could provide new options for people suffering from treatment-resistant uterine cancer, according to new Yale School of Medicine (YSM) research.

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.

Now, a new study published May 14 in Clinical Cancer Research suggests that doctors could use sacituzumab govetican—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.”

Around 3% of all women will develop uterine cancer in their lifetimes. The National Institutes of Health estimate that around 68,000 Americans will be diagnosed with uterine cancer in 2026. And while the majority will survive treatment, over 14,400 are estimated to 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.

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

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 govetican 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 govetican compared with standard chemotherapy in a larger group of patients. This trial is part of a larger trend towards 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 govetican that target a specific protein biomarker on cancer cells are “the future of oncology.”