People with advanced or recurrent endometrial cancer whose tumors are mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) may have better long-term outcomes when chemotherapy is combined with the PD-1 inhibitor dostarlimab-gxly (Jemperli), according to updated results from a phase 3 clinical trial.

Among the study group, 72.8 percent of people who received dostarlimab plus carboplatin and paclitaxel were alive at four years, compared with 40.3 percent of those who received chemotherapy alone.

Between one-quarter and one-third of endometrial cancers are dMMR or MSI-H, meaning these findings could apply to a significant group of people living with the condition.

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🗳️ Have you had your tumor tested for dMMR or MSI-H biomarkers?

Yes, and my tumor is dMMR or MSI-H.

Yes, and my tumor is neither dMMR nor MSI-H.

No, but I plan to ask about testing.

No, and I don’t plan to ask about testing.

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What Is Dostarlimab?

Dostarlimab is an immunotherapy drug called a PD-1 inhibitor. It works by blocking a signal that can let cancer cells hide from immune cells. This helps the immune system better recognize and attack the cancer.

Carboplatin and paclitaxel are chemotherapy drugs that kill fast-growing cells in a different way. So the combination is designed to attack the cancer from more than one angle.

The U.S. Food and Drug Administration (FDA) first approved dostarlimab in April 2021 for dMMR endometrial cancer. The agency later expanded approval of this combination in August 2024 for adults with primary advanced or recurrent endometrial cancer. Treatment starts with dostarlimab plus carboplatin and paclitaxel, followed by dostarlimab alone.

What Do dMMR and MSI-H Mean?

The new findings apply to a specific subtype of endometrial cancer. Tumors described as dMMR or MSI-H contain cancer cells that have trouble repairing damaged DNA, which may make them more likely to respond to immunotherapy.

What the Study Found

Researchers looked at long-term results from the study participants with dMMR/MSI-H endometrial cancer after around 56 months. There were 118 people with confirmed dMMR/MSI-H tumors, split between those taking dostarlimab-plus-chemotherapy and those taking chemotherapy alone.

The researchers found:

• People in the dostarlimab group had four-year overall survival of 72.8 percent, compared to 40.3 percent with chemotherapy alone. In other words, nearly 73 percent of people who received dostarlimab plus chemotherapy were alive four years after starting treatment.
• Four-year progression-free survival was 57.9 percent with dostarlimab and 15.7 percent with chemotherapy alone. This means that nearly 58 percent of people in the dostarlimab group were alive without their cancer worsening at the four-year mark.
• A median overall survival rate had not yet been reached in the dostarlimab group because more than half of the participants were still alive when the data was analyzed. In the chemotherapy-alone group, median overall survival was 32.8 months.

Researchers also used a statistical method called a mixture cure model. In that analysis, 54 percent of people in the dostarlimab group were estimated to have curative potential (meaning their disease may not progress over a long period of time). That does not mean 54 percent were cured, but it does suggest the benefit may be long-lasting for some people.

No new safety concerns were identified during the longer follow-up. However, as with all treatments, both dostarlimab and chemotherapy drugs can cause side effects. It’s important to always discuss all side effects with your healthcare team when exploring potential treatment options.

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On MyEndometrialCancerTeam, people share their experiences with endometrial cancer, get advice, and find support from others who understand.

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