Study: New treatment option for advanced or recurrent endometrial cancer
If you have advanced or recurrent endometrial cancer, there is a new treatment called Jemperli (dostarlimab) that could be an option for you. This study looked at how well Jemperli worked compared to standard treatment. Based on these results, the Food and Drug Administration (FDA) approved the combination of Jemperli and chemotherapy for certain types of advanced endometrial cancer. (Posted 8/4/23)Printer Friendly Page Read the Original Article
Most relevant for: People with advanced or recurrent endometrial cancer. It may also be relevant for:
- people with endometrial cancer
- people with metastatic or advanced cancer
Strength of Science: High
Research Timeline: Post Approval
What is this research about?
Researchers wanted to see how well an called Jemperli (dostarlimab) works when combined with chemotherapy for treating advanced or recurrent endometrial cancer.
Why is this study important?
Chemotherapy is the standard treatment for advanced or recurrent endometrial cancer. Unfortunately, long-term survival rates with this treatment remain low.
This study showed that Jemperli plus chemotherapy is a new treatment option for some patients with advanced or recurrent endometrial cancer. Jemperli plus chemotherapy can increase the time before cancer comes back and lengthen survival for people with endometrial cancer. The combination worked particularly well for participants whose tumors had a marker called MSI-H or (mismatch repair deficient). Based on these results, the Food and Drug Administration () approved the combination of Jemperli and chemotherapy to treat newly diagnosed advanced or recurrent or MSI-H endometrial cancer.
Almost 500 people with advanced or recurrent endometrial cancer were included in this study. They were placed in two groups:
- half had chemotherapy.
- half had chemotherapy plus Jemperli.
At the two-year time point in the study, among all participants:
- fewer people in the Jemperli-plus-chemotherapy group had their cancer get worse or come back than the group that received chemotherapy alone.
- more people survived in the group that received Jemperli-plus-chemotherapy than in the group that received chemotherapy alone. This data is still being collected and these numbers may change.
Jemperli plus chemotherapy worked particularly well for participants with MSI-H or cancers.
Among those whose tumor was MSI-H or dMMR:
- half as many people who took Jemperli plus chemotherapy had their cancer return compared to people who took chemotherapy alone.
|% of people whose cancer came back after 2 years|
|Treatment||with any tumor type||with MSI-H tumors|
|Jemperli + chemo||64%||39%|
A similar trial (NRG-GY018) tested a related drug called Keytruda (pembrolizumab) combined with chemotherapy. While the NRG-GY018 trial only has results for 1 year after treatment, their results were similar. Keytruda plus chemotherapy improved outcomes for those with endometrial cancer. Together these studies support the use of combining an drug with chemotherapy for initial treatment of advanced or recurrent endometrial cancer.
The most common side effects in this study were nausea, hair loss and fatigue. Most side effects occurred as often in people treated with Jemperli plus chemo as in those treated with chemo only. This suggests that these side effects are caused by chemotherapy. Nausea and rash were slightly more common in those who took Jemperli plus chemo.
Quality of life
Patients in each group were asked about their quality of life by rating their pain, fatigue, and how well they felt physically, emotionally and socially. People in both groups reported similar overall quality of life.
What does this mean for me?
If you have advanced or recurrent endometrial cancer, you should discuss this research with your doctor. Ask whether your cancer was tested for the markers MSI-H or and whether adding Jemperli or another drug to your treatment is an option for you.
Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. The New England Journal of Medicine; 2023; doi: 10.1056/NEJMoa2216334
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
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- Is the addition of Jemperli or Keytruda to my treatment an option?
- Does my tumor have any markers (such as, or ) that could guide treatment decisions?
- How long does treatment with Jemperli last, and how often would I need to receive it?
- What is the estimated cost of Jemperli treatment? is it covered by my insurance?
- Are there any specific precautions I need to consider when taking Jemperli?
- Can Jemperli interact with any of my other medications or treatments?
- What are the chances of recurrence or progression of my cancer even with the addition of Jemperli?
The National Comprehensive Cancer Network (NCCN) provides expert-developed guidelines for tumor testing of people with endometrial cancer.
- MMR and/or MSI tumor testing should be performed on all endometrial cancer tumors.
- Depending on MMR/MSI results, referral for genetic counseling to test for .
- Tumor testing for estrogen-receptor status (ER-positive or ER-negative) is recommended for 3, 4 () or recurrent endometrial cancer.
- testing is recommended for advanced or recurrent cancers.
- Consider testing for NTRK gene fusion for or recurrent endometrial cancer.
- Consider (TMB) testing.
The following resources can help you locate an expert near you.
Finding gynecologists with expertise in cancer risk and treatment
- The Foundation for Women's Cancer has a search tool to help you find a gynecologic oncologist.
Some symptoms and conditions related to female reproduction may be managed by other experts.
- The Oncofertility Consortium maintains a national database of healthcare providers with expertise in fertility preservation and treatment of people who are diagnosed with cancer or have a high risk for cancer due to an .
- Livestrong has a listing of 450 sites that offer fertility preservation options for people diagnosed with cancer.
Financial assistance may be available to make the cost of fertility preservation affordable for more patients. Patients are referred to those programs as needed.
- The North American Menopause Society has a tool to help you find a qualified menopause expert in your area.
Sexual health experts
- The Sexual Medicine Society of North America (SMSNA) has a search tool to find experts in your area who provide sexual health care services.
- The American Association of Sexuality Educators, Counselors and Therapists (AASECT) maintains a tool to help people find a sexual health expert near them.
Other ways to find experts
- The National Cancer Institute (NCI)-designated comprehensive cancer centers deliver cutting-edge cancer care to patients in communities across the United States. Most centers have specialized screening and prevention centers for high-risk people. Find a center near you and learn about its specific research capabilities, programs, and initiatives.
- Register for the FORCE Message Boards to get referrals from other members. Once you register, you can post on the Find a Specialist board to connect with other people who share your situation.
IN-DEPTH REVIEW OF RESEARCH
Endometrial cancer is the second most common gynecologic cancer and the sixth most common cancer among women worldwide. The standard chemotherapy for treating primary advanced or recurrent endometrial cancer is usually a combination of carboplatin and paclitaxel. Unfortunately, long-term survival rates for this cancer remain low; median overall survival is less than three years.
Specific types of endometrial cancer known as mismatch repair-deficient () and microsatellite instability-high (MSI-H) account for about 25 to 30 percent of all cases. These tumors have increased expression of the protein PD-1 receptor and its binding partners and PD-L2, as well as a high (frequent mutations occur within the tumor). These characteristics make them potentially responsive to immunotherapies that target these immune checkpoints. MSI-H and cancers are common in people with but may also occur spontaneously.
Jemperli (dostarlimab) is an immune-checkpoint inhibitor that targets the PD-1 receptor. Based on the results of the GARNET trial, Jemperli received approval in the European Union for treating dMMR-MSI-H advanced or recurrent endometrial cancer. It is also approved in the United States for advanced . The GARNET trial demonstrated long-lasting anti-tumor activity in patients with mismatch repair-proficient (pMMR), microsatellite-stable (MSS) tumors, although the response rates were lower compared to patients with dMMR-MSI-H tumors.
Combining chemotherapy with can improve the effects of each separate treatment by disrupting immunosuppressive pathways and enhancing the cytotoxic T-cell response in the tumor microenvironment. This combination has clinical benefits and improved survival in several cancer types. In the RUBY trial, researchers looked at the usefulness and safety of Jemperli plus carboplatin and paclitaxel compared to plus carboplatin and paclitaxel in patients with primary advanced or recurrent endometrial cancer.
Researchers of this study wanted to know
The researchers wanted to test the usefulness of Jemperli for the treatment of primary advanced or recurrent endometrial cancer. They evaluated its ability to shrink tumors and improve outcomes in patients with this type of cancer.
Populations looked at in this study
The study focused on people with primary advanced or recurrent endometrial cancer. Most patients were white and in their early-to-mid-60s.
The study used a phase 3, global, double-blind, , clinical trial design to investigate the effects of Jemperli on primary advanced or recurrent endometrial cancer. Participants included 494 people diagnosed with primary 3 or 4 endometrial cancer or first recurrent endometrial cancer; they were randomly assigned to either Jemperli (500mg) or plus carboplatin and paclitaxel every three weeks. They were then given a higher dose of Jemperli (1,000 mg) or every six weeks for up to three years. The study team measured whether the patients’ cancers progressed during this timeframe and if any safety issues occurred.
Of the 494 patients, 23.9 percent had tumors with () or microsatellite instability-high ().
Those tumors that were dMMR/MSI-high had a dramatically better response to Jemperli than those taking the progression-free survival (PFS) at 24 months was:
- 61.4 % for Jemperli.
- 15.7 % for .
When looking at all patients, those taking Jemperli responded to treatment more often than those taking the placebo; PFS at 24 months was:
- 36.1 % for Jemperli.
- 18.1 % for .
At 24 months, overall survival was:
- 71.3 % for Jemperli
- 56.0 % for .
The most common adverse events during treatment were nausea, alopecia (hair loss) and fatigue and often occur with chemotherapy treatment. Nausea and rash were more slightly more common in those who took Jemperli than .
These results indicate that Jemperli is a promising treatment option for primary advanced or recurrent endometrial cancer. This combination of Jemperli and chemotherapy demonstrated the potential to shrink tumors and improve survival.
Strengths and limitations
- The study compared two groups, one that received Jemperli and chemotherapy, and one that received chemotherapy and a . This study design strengthens the findings.
- The number of participants was small and did not include a lot of people of different races or ethnicities. Follow-up research with a larger, more diverse group is needed to determine whether the addition of Jemperli would benefit all patients with advanced or recurrent endometrial cancer.
This study suggests that Jemperli is a promising treatment option for primary advanced or recurrent endometrial cancer. Further research is needed to confirm and expand upon these findings. If you are considering treatment options for primary advanced or recurrent endometrial cancer, ask your healthcare providers if adding Jemperli (dostarlimab) or another drug to your treatment regimen is an option for you.
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The following studies are enrolling people with advanced endometrial cancer.
- NCT04486352: A Study of Targeted Therapies for Patients With Recurrent Endometrial CancerA Study of Targeted Therapies for Patients With Recurrent Endometrial Cancer. This study is to test the safety and effectiveness of different kinds of with or without atezolizumab in people with recurrent endometrial cancer.
- NCT05173987: Comparing an Drug, Pembrolizumab With Chemotherapy in Advanced or Recurrent Endometrial Cancer. This study will test the safety and effectiveness of treatment with pembrolizumab, compared to a combination of chemotherapy in women with advanced or recurrent endometrial cancer who had not previously been treated with chemotherapy.
- NCT03607890: Nivolumab and Relatlimab in Advanced MSI-H Cancers Resistant to Prior PD-(L)1 Inhibitor. This study will evaluate the safety, effectiveness, and tolerability of the drugs nivolumab and relatlimab in patients with -high (MSI-H) resistant to prior PD-(L)1 therapy.
- NCT03955978: Dostarlimab in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial Cancer. The purpose of this study is to evaluate dostarlimab compared to standard-of-care radiation therapy for patients with inoperable endometrial cancer to establish the safety and efficacy of inducing an anti-tumor immune response.
- NCT04463771: Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy. (POD1UM-204). This is a Phase 2 study of the PD-1 antibody retifanlimab in participants who have advanced or endometrial cancer that has progressed on or after platinum-based chemotherapy.
A number of other clinical trials for patients with endometrial cancer can be found here.
The following organizations offer peer support services for people with or at high risk for endometrial cancer:
- FORCE peer support
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Private Facebook Group.
- Virtual and in-person support meetings.
- Join a Zoom community group meeting.
- SHARE is a nonprofit that provides support and information for women with breast, ovarian or endometrial cancer.
ECANA is an online resource for Black people with endometrial cancer.
Who covered this study?
Mansoor R. Mirza, MD, on Endometrial Cancer: New Findings on Dostarlimab-gxly Plus Chemotherapy This article rates 4.0 out of 5 stars
Data confirm benefit of dostarlimab regimen for women with advanced endometrial cancer This article rates 4.0 out of 5 stars
FDA Prioritizes GSK's Breakthrough Drug Jemperli for Endometrial Cancer Treatment, a First in Decades This article rates 3.0 out of 5 stars