Sacituzumab tirumotecan endometrial cancer trial shows promise

A large international trial has found that a targeted drug can slow the return of advanced endometrial cancer and lower the risk of death after earlier treatment stops working. The sacituzumab tirumotecan endometrial cancer trial compared the drug, known as sac-TMT, with standard chemotherapy in women whose cancer had advanced or returned after chemotherapy and immunotherapy. Results were presented at the annual meeting of the European Society for Medical Oncology and published online in The Lancet, according to researchers at NYU Langone Health and its Perlmutter Cancer Center. Endometrial cancer affects the inner lining of the uterus and is the most common cancer of the female reproductive system, yet options remain limited when the disease is found late or comes back after initial treatment.

How the drug works

Sac-TMT belongs to a class of treatments called antibody-drug conjugates, which carry a cell-killing chemical directly to tumor cells instead of exposing the whole body to the same dose. The drug latches onto Trop-2, a protein found in abundance on the surface of endometrial cancer cells, and then releases its payload inside the cell. That targeted approach is designed to damage tumors while limiting harm to healthy tissue, a balance that matters in treatment after several earlier therapies. The sacituzumab tirumotecan endometrial cancer trial, formally called TroFuse-005/ENGOT-en23/GOG-3095, enrolled patients at cancer centers across Europe, Asia and North America.

Patients enrolled at more than 200 cancer centers in 29 countries, and most were followed for at least a year after joining the trial and being assigned to a treatment group. Everyone in the study had already received pembrolizumab, an immunotherapy drug sold as Keytruda that helps the immune system recognize cancer cells. The comparison mattered because, until now, no standard therapy existed to prevent or delay a return of the disease after that sequence of chemotherapy and immunotherapy. Researchers set out to test whether the sacituzumab tirumotecan endometrial cancer treatment given at that point could change the course of a recurrence.

What the trial found

In the sacituzumab tirumotecan endometrial cancer trial, 386 women were assigned to receive sac-TMT after immunotherapy, while 390 received chemotherapy alone after immunotherapy. The gap in outcomes was clear in the main measures the researchers tracked. Women given sac-TMT had a 41% lower risk of their cancer progressing, meaning growing or spreading, than women given chemotherapy. Their overall risk of death was 32% lower than in the chemotherapy group. Tumor shrinkage and other responses were also more common with the targeted drug, at 35.1% compared with 17.3% for chemotherapy.

Side effects were a real part of the picture, and the researchers described them as manageable. The most frequent problems in the sac-TMT group were low blood counts, including anemia and neutropenia, inflammation in the mouth, and dry or itchy eyes. Three patients in each treatment group died during follow-up, according to the report. The pattern of side effects in the sacituzumab tirumotecan endometrial cancer study will matter to doctors weighing the drug for patients who have already been through chemotherapy and immunotherapy, since tolerability shapes whether a treatment can be continued long enough to help.

Why the findings matter

The results land against a difficult background. Death rates from uterine cancers in the United States have risen to more than fourteen thousand each year, with an estimated 68,000 newly diagnosed cases in the latest annual estimate cited by the researchers. Study co-investigator Michelle Lightfoot, a gynecologic oncologist at Perlmutter Cancer Center, said aggressive subtypes of the disease are more commonly seen in Black patients, who face twice the risk of dying from it. The sacituzumab tirumotecan endometrial cancer results suggest antibody-drug conjugates such as sac-TMT are effective against those aggressive cancers, delaying progression and prolonging survival when the disease returns, according to the researchers.

Principal investigator Bhavana Pothuri, a professor at NYU Grossman School of Medicine, said the positive results establish sac-TMT as a new standard treatment for recurrent endometrial cancer and that clinical guidelines will need reassessment to include it. The sacituzumab tirumotecan endometrial cancer findings also point beyond a single disease, since the same surface protein is overexpressed in tumors of the lungs, breasts, ovaries and intestines. Researchers said that pattern raises the possibility of testing the drug in other cancers where the protein is abundant, although that work remains ahead. For patients facing a recurrence now, the trial offers a targeted option tested after immunotherapy, with measured gains in slowing progression and extending life.

Coverage of the sacituzumab tirumotecan endometrial cancer findings was reported by MedicalXpress, and the New York Post also covered the trial results. The underlying study appears in The Lancet.

GenZNewz has also covered targeted cancer trials, including the divarasib lung cancer trial and a lung cancer combination that cut death risk by half.