{"id":28772,"date":"2023-04-12T12:00:00","date_gmt":"2023-04-12T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2023\/immunotherapy-endometrial-cancer-pembrolizumab-dostarlimab"},"modified":"2024-11-03T15:12:48","modified_gmt":"2024-11-03T15:12:48","slug":"immunotherapys-role-in-treating-endometrial-cancer-expected-to-grow","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/immunotherapys-role-in-treating-endometrial-cancer-expected-to-grow\/","title":{"rendered":"Immunotherapy\u2019s Role in Treating Endometrial Cancer Expected to Grow"},"content":{"rendered":"

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Results from two large clinical trials show that adding immunotherapy to standard treatment for advanced endometrial cancer, including people with stage III disease (above), improves progression-free survival. <\/p>\n

Credit: Cancers November 2021. https:\/\/doi.org\/10.3390\/cancers13225848. CC BY 4.0.<\/p>\n<\/p><\/div>\n<\/figcaption><\/figure>\n<\/p><\/div>\n

Immunotherapy is likely to become a much more common treatment for women with advanced endometrial cancer, following the release of results from two large clinical trials. <\/p>\n

In both trials, combining drugs known as immune checkpoint inhibitors<\/a> with standard chemotherapy substantially increased how long some people with endometrial cancer lived without their cancer getting worse, a measure called progression-free survival<\/a>. The improvement in progression-free survival was greatest in people whose tumors had specific genetic changes called dMMR or MSI<\/a>-high.<\/p>\n

Results from both studies were presented at the 2023 annual meeting of the Society of Gynecologic Oncology (SGO) on March 27 and published simultaneously in the New England Journal of Medicine<\/em>.<\/p>\n

The trials used different immune checkpoint inhibitors\u2014pembrolizumab (Keytruda)<\/a> and dostarlimab (Jemperli)<\/a>\u2014and had some other differences in how they were conducted. But the researchers who led the trials and other experts agreed that the findings should change the treatment for people with advanced endometrial cancer and those who initially had endometrial cancer that came back, or recurred<\/a>, after treatment.<\/p>\n

\u201cBoth of these trials hit a home run,\u201d said Rebecca Arend, M.D., who specializes in treating gynecologic cancers at the University of Alabama at Birmingham O\u2019Neal Comprehensive Cancer Center. \u201cOverall, this is a huge win for our patients,\u201d Dr. Arend added during a session on both trials at the SGO meeting.<\/p>\n

Neither drug is yet approved by the Food and Drug Administration (FDA) for this specific use. And some gynecologic cancer<\/a> researchers stressed that there\u2019s still more to learn about how best to use immune checkpoint inhibitors to treat endometrial cancer.<\/p>\n

For example, the trial that tested dostarlimab, called RUBY, hasn\u2019t gone on long enough yet to show whether adding the drug to chemotherapy improves how long participants live overall, cautioned Elise Kohn, M.D., of NCI\u2019s Division of Cancer Treatment and Diagnosis<\/a>, who specializes in treating gynecologic cancers. Dr. Kohn spoke at a different meeting on March 27, a virtual plenary session held by the European Society for Medical Oncology (ESMO) that focused on the RUBY trial results. The same holds true for NRG-GY018, other experts noted.<\/p>\n

RUBY\u2019s findings, as well as those from several other recent studies, she continued, also suggest that even dMMR endometrial cancers may have important biological differences that may influence whether and the extent to which immunotherapy will work for them.<\/p>\n

Nevertheless, Dr. Kohn said, both trials\u2019 findings have \u201cpresented \u2026 new opportunities\u201d to improve the treatment of endometrial cancer.<\/p>\n

Improving outcomes for advanced endometrial cancer<\/h2>\n

The number of US women diagnosed each year with endometrial cancer has been steadily growing, and it is the only gynecologic cancer with rising death rates.<\/p>\n

The increased incidence<\/a> has been linked with several factors, including the obesity epidemic<\/a>, while the increasing death rate has been attributed to more women being diagnosed with aggressive forms of the disease<\/a> than in the past.<\/p>\n

Still, most women are diagnosed with endometrial cancer when it\u2019s still early stage<\/a>, and about 95% of women diagnosed with early-stage disease will live for at least 5 years. <\/p>\n

But the long-term outlook for women who are diagnosed with endometrial cancer when it has already spread, or metastasized<\/a>, beyond the uterus is much less favorable: less than 20% survive for 5 years or more. The long-term prognosis for women with recurrent endometrial cancer is also poor.<\/p>\n

The combination of the chemotherapy drugs cisplatin and paclitaxel has long been the standard treatment<\/a> for women with advanced or recurrent endometrial cancer. But treatment options for these two groups of patients have changed recently, largely because of advances in immunotherapy. <\/p>\n

Over the last 2 years, pembrolizumab and dostarlimab were approved by the Food and Drug Administration (FDA) to treat women with advanced or recurrent endometrial cancer whose disease had worsened after initial, or first-line, treatment with chemotherapy.<\/p>\n

The results from the clinical trials that led to those approvals set the stage for trials to test whether adding an immune checkpoint inhibitor as part of initial treatment might further extend how long women live without their cancer getting worse and, potentially, overall.<\/p>\n

Improved progression-free survival, especially for dMMR tumors<\/h2>\n

The trial that used pembrolizumab, called NRG-GY018, included more than 800 participants<\/a>. They were randomly assigned to receive either pembrolizumab plus chemotherapy for about 6 months, followed by \u201cmaintenance<\/a> treatment\u201d with pembrolizumab alone for about 21 months or to receive chemotherapy plus a placebo, followed by a placebo alone using the same schedule.<\/p>\n

The NRG-GY018 study was supported by NCI, with some funding from Merck, which manufactures pembrolizumab, as part of a formal research agreement.<\/p>\n

About 30% of people in NRG-GY018 had dMMR tumors. Among the dMMR group, 74% of participants treated with pembrolizumab were alive without their cancer getting worse 12 months after starting treatment, compared with 38% of those in the placebo group. In the pMMR group, those numbers were 50% and 30%, respectively.<\/p>\n

The data were presented by the trial\u2019s lead investigator, Ramez Eskander, M.D., of the John and Rebecca Moores Comprehensive Cancer Center in San Diego. <\/p>\n