Study: Immunotherapy improves outcomes of advanced endometrial cancer

Relevance: High

Strength of Science: High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

Researchers wanted to assess the usefulness of the immunotherapy drug Keytruda (pembrolizumab) when it is combined with chemotherapy for treating advanced or recurrent endometrial cancer. This study compared the outcomes of people who received a combination of Keytruda plus chemotherapy to people who only received chemotherapy.

Why is this study important?

The number of cases and deaths from endometrial cancer are increasing in the United States. This is especially true among Black women (see our XRAY review here). Currently, chemotherapy is the standard treatment for advanced or recurrent endometrial cancer. Unfortunately, long-term survival rates with this treatment remain low.

This study found that Keytruda plus chemotherapy increased the time before cancer came back compared to chemotherapy alone. The results of this and similar studies (see our XRAY review on a similar study here) will likely change the treatment for people who are newly diagnosed with advanced endometrial cancer.

Study findings

Just over 800 people with advanced or recurrent endometrial cancer were included in this study. Participants were placed in two groups:

• Half of the participants received chemotherapy only.
• Half of the participants received chemotherapy plus Keytruda.

After the 1-year time point in the study, among all participants:

• Fewer people in the Keytruda-plus-chemotherapy group had cancer that worsened or came back than the group that received chemotherapy alone.
• More people survived in the group that received Keytruda plus chemotherapy than in the group that received chemotherapy alone.

Mismatch repair

Doctors test pieces of tumors in labs to find  features (called biomarkers) that may help guide treatment.

Mismatch repair is a biomarker that measures how well cancer cells can repair certain types of DNA damage.  

• Some endometrial cancers are mismatch repair deficient (dMMR), which means that the cancer cells cannot repair certain types of DNA changes. Cancers with dMMR are common among people with Lynch Syndrome.
• Some endometrial cancers are mismatch repair proficient (pMMR), which means that cancer cells can repair certain types of DNA changes.

Keytruda plus chemotherapy worked particularly well for people with dMMR cancers.

• After one year, people with dMMR-advanced or dMMR-recurrent endometrial cancer who had Keytruda plus chemotherapy were 70% less likely to have a recurrence or die.
• After 8 months, people with pMMR-advanced or PMMR-recurrent endometrial cancer who had Keytruda plus chemotherapy were 46% less likely to have a recurrence or die.

Side effects

Nearly everyone in the trial reported side effects of some kind. The most common side effects included:  

• mild fatigue
• numbness or pain in the hands or feet (neuropathy)
• a lower-than-normal amount of red blood cells (anemia)
• nausea
• constipation
• diarrhea

These side effects are similar to what would be expected for people receiving chemotherapy, even without the addition of immunotherapy.

Serious side effects occurred in a few participants, regardless of their treatment or whether they had dMMR tumors or pMMR tumors. These side effects included:

• hypo or hyperthyroidism (too much or too little thyroid hormone)
• heart attacks
• infections in the blood
• blockage of the intestines

Immunotherapy and endometrial cancer

Keytruda is a type of immunotherapy drug known as an immune checkpoint inhibitor. This class of immunotherapy drugs works by helping the body’s immune system find and destroy cancer cells. Immune checkpoint inhibitors are effective for a wide range of cancers. This study adds additional support for the use of this type of immunotherapy together with chemotherapy as a treatment for advanced or recurrent endometrial cancer.

What does this mean for me?

If you have been diagnosed with advanced endometrial cancer, ask your healthcare providers about treatment with Keytruda plus chemotherapy instead of chemotherapy alone.

If you have already received treatment for advanced endometrial cancer and your cancer has come back, Keytruda might still be an option for you. In this study, people who already had radiation, hormone therapy or chemotherapy one year prior to the study benefitted from adding Keytruda to chemotherapy.

Recently, the Food and Drug Administration (FDA) approved the combination of a similar immunotherapy drug called Jemperli with chemotherapy for certain types of advanced endometrial cancer. You can read more about this approval in our XRAY review here.

Reference

Eskander RN, Sill MW, Beffa L, et al., Pembrolizumab plus chemotherapy in advanced endometrial cancer. New England Journal of Medicine; 2023; 388:2159-2170. Published online March 27, 2023.

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 12/4/23