Update: News from the FDA: New endometrial cancer approvals

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Research Timeline: Post Approval

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The FDA recently approved three new drugs for treating endometrial cancer. All three are a type of treatment known as immunotherapy. These work by increasing the immune system's ability to attack cancer cells. A short video about how this type of drug works is found here.

These drugs benefit people with tumors that are MSI-H or dMMR (mismatch repair deficient). People with Lynch syndrome (due to inherited mutations in MLH1, MSH2, MSH6 or PMS2) often have dMMR tumors, although people without Lynch syndrome can also have dMMR tumors. New findings show that these drugs may also benefit people with pMMR (mismatch repair proficient) tumors.

New approval for Jemperli
What is this update about?

In August 2024, the FDA granted accelerated approval of Jemperli with chemotherapy for anyone with primary advanced or recurrent endometrial cancer.

Why is this update important?

In July 2023, the FDA approved the drug Jemperli (dostarlimab) with chemotherapy for treating certain types of endometrial cancer. This approval was based on the RUBY study. While this study showed that Jemperli increased the average time until cancer returned or worsened for all participants, this initial approval was only for people whose tumors had a marker called MSI-H or dMMR (mismatch repair deficient). To see FORCE’s initial XRAY review on this drug, click here.

The more recent approval expands the use of Jemperli with chemotherapy to anyone with advanced or recurrent endometrial cancer. Its use is no longer limited to people whose tumors are MSI-H or dMMR.

New approval for Imfinzi
What is this update about?

Studies have explored combining Imfinzi (durvalumab) with other therapies, such as chemotherapy or PARP inhibitors.

Previously, Imfinzi has been approved in combination for some non-small cell lung cancers; biliary tract cancers, including cholangiocarcinoma; gallbladder cancer and kidney cancer.

On July 14, 2024, the FDA approved Imfinzi (durvalumab) with chemotherapy for people who have primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). Following this combination treatment, Imfinzi can be used alone.

This approval is based on one part of the DUO-E trial. This specific part looked at the effectiveness of combining Imfinzi with chemotherapy as a treatment for endometrial cancer.

Imfinzi plus chemotherapy followed by maintenance therapy with Imfinzi alone increased the time until cancer returned. For participants who had chemotherapy alone, the average time until cancer returned was 12.6 months compared to 15.4 months for patients who had both Imfinzi and chemotherapy.

People who benefitted most from this combination had tumors that were dMMR. In the 95 people with dMMR tumors, the average time until cancer returned has not yet been determined (the cancers of study participants still have not returned) compared to about seven months for people who had chemotherapy alone. Overall survival is not yet known.

Why is this update important?

The study found that combining Imfinzi with chemotherapy followed by maintenance therapy with Imfinzi alone increased the average time until cancer returned, particularly among people whose tumors were dMMR.

Because Imfinzi increased the time until cancer returned for everyone who took it, like Jemperli, it may be approved in the future to treat all primary advanced or recurrent endometrial cancer regardless of MMR status.

New approval for Keytruda
What is this update about?

On June 17, 2024, the FDA approved Keytruda (pembrolizumab) in combination with chemotherapy, followed by Keytruda alone for adults with primary advanced or recurrent endometrial cancer.

This approval was due to the results of the KEYNOTE-868/NRG-GY018 trial. The trial enrolled 810 people with advanced or recurrent endometrial carcinoma. Two groups were included: the mismatch repair deficient (dMMR) group and the mismatch repair proficient (pMMR) group.  There were 222 people in the dMMR group and 588 patients in the pMMR group. Participants received either Keytruda plus chemotherapy followed by Keytruda alone or a sugar pill (placebo) plus chemotherapy.

Researchers looked at the time until cancer returned or worsened.

In the dMMR group, the time until cancer returned is not yet known among those who had Keytruda plus chemotherapy. The average time until cancer returned was 6.5 months among those who had chemotherapy only.

In the pMMR group, the average time until cancer returned was 11.1 months among those who had Keytruda and 8.5 months among those who had chemotherapy only.

Why is this update important?

The KEYNOTE study found that the combination of Keytruda and chemotherapy followed by Keytruda alone offers significant benefits for patients with advanced endometrial cancer, regardless of MMR status. These benefits included increased time until cancer returned and overall survival compared to chemotherapy alone.

What does this mean for me?

Jemperli
If you or a family member has endometrial cancer, and you have not been a candidate for Jemperli plus chemotherapy, you may want to speak to your healthcare providers about your current options. A year ago, before the FDA expanded its use, this combination was not approved for all types of endometrial cancer.

Imfinzi
If you have recurrent or primary advanced endometrial cancer with a tumor marker called dMMR, you might be eligible for Imfinzi plus chemotherapy followed by Imfinzi alone (maintenance therapy).

Research studies such as the DUO-E trial are assessing different drug combinations. Researchers want to know if combinations can better treat cancer when drugs address multiple cancer pathways.

Keytruda
Keytruda is currently used to treat various types of cancer, including melanoma, lung, kidney, bladder and triple-negative breast cancers. It is also used to treat some head and neck cancers and colorectal cancers.

Keytruda alone has also been approved for people with advanced endometrial cancer that is MSI-H or dMMR.

Keytruda is now approved for advanced endometrial cancer, regardless of MMR or MSI status. If you have recurrent or advanced endometrial cancer and have not found an effective treatment, you may be a candidate for Keytruda combined with chemotherapy.

Reference

FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy. FDA News release. August 1, 2024.

FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. FDA News release. June 14, 2024.

FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. FDA News release. June 17, 2024.  

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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posted 11/7/24