Study: New treatment option for advanced or recurrent endometrial cancer

IN-DEPTH REVIEW OF RESEARCH

Study background

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 (dMMR) 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 PD-L1 and PD-L2, as well as a high tumor mutational burden (frequent mutations occur within the tumor). These characteristics make them potentially responsive to immunotherapies that target these immune checkpoints. MSI-H and dMMR cancers are common in people with Lynch syndrome 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 dMMR advanced solid tumors. 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 immunotherapy 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 placebo 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.

Study design

The study used a phase 3, global, double-blind, randomized, placebo-controlled clinical trial design to investigate the effects of Jemperli on primary advanced or recurrent endometrial cancer. Participants included 494 people diagnosed with primary stage 3 or 4 endometrial cancer or first recurrent endometrial cancer; they were randomly assigned to either Jemperli (500mg) or placebo plus carboplatin and paclitaxel every three weeks. They were then given a higher dose of Jemperli (1,000 mg) or placebo 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.

Study findings

Of the 494 patients, 23.9 percent had tumors with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-high).

Those tumors that were dMMR/MSI-high had a dramatically better response to Jemperli than those taking the placebo progression-free survival (PFS) at 24 months was:

• 61.4 % for Jemperli.
• 15.7 % for placebo.

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 placebo.

At 24 months, overall survival was:

• 71.3 % for Jemperli
• 56.0 % for placebo.

 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 placebo.

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

Strengths

• The study compared two groups, one that received Jemperli and chemotherapy, and one that received chemotherapy and a placebo. This study design strengthens the findings.

Limitations

• 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.

Conclusions

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 immunotherapy drug to your treatment regimen is an option for you.

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posted 8/4/23