Is lenvatinib / pembrolizumab used in endometrial cancer?

Key Points

• Yes, the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) was approved in September 2019 for the treatment of endometrial cancer.
• It is used to treat patients with advanced endometrial cancer that is not MMR deficient (dMMR) or MSI high (MSI-H) after at least one other drug treatment has been tried.
• This combination is used in patients who are not candidates for surgery that will cure the cancer or radiation treatment.

Lenvatinib is considered a targeted drug therapy and pembrolizumab is an immunotherapy agent. These drugs can work together in different ways to help treat advanced endometrial cancer.

• Lenvatinib is a kinase inhibitor that inhibits endothelial growth factor (VEGF) receptors VEGFR1, VEGFR2, and VEGFR3. Lenvatinib blocks proteins on cells and signals directed at blood vessels to help slow down the growth and spread of certain types of cancer.
• Pembrolizumab is known as an Immune Checkpoint Inhibitor. It blocks the PD-1 (programmed death receptor-1) pathway to help prevent cancer cells from hiding from the immune system.

How do I know if I have a MSI-H/dMMR cancer?

In the body, the DNA mismatch repair (MMR) system helps to correct errors that may occur during DNA replication. Problems with the MMR system can lead to microsatellite instability-high (MSI-H). These types of cancers have errors in their generic sequences that may be repeated (called microsatellites). MSI-H/dMMR may occur when a cell is unable to repair these errors made during division.

To find out if you have cancer that contains a biomarker for MSI-H/dMMR, a sample of tissue is taken and a test is ordered that will examine your tissue. Many types of cancer are examined for MSI-H/dMMR biomarkers. Roughly 75% of endometrial cancer cases are not microsatellite instability-high or mismatch repair deficient.

Women with endometrial cancer are eligible for lenvatinib plus pembrolizumab if:

• the tumors are NOT MSI-H or dMMR
• they cannot have curative surgery or radiation treatment
• their disease has progressed after other systemic therapies

Studies are ongoing to determine the effectiveness of lenvatinib plus pembrolizumab regardless of tumor MSI status.

In March 2022, pembrolizumab (Keytruda) as a single agent (called monotherapy) was approved for treatment of patients with advanced endometrial carcinoma that IS microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-approved test. In addition, these patients have had disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Related questions

• What is the success rate of Keytruda?
• How long does it take for Keytruda to work?
• What are monoclonal antibodies?

What are the study results for lenvatinib / pembrolizumab?

Lenvatinib plus pembrolizumab was evaluated in a study (KEYNOTE-146) with 94 patients with metastatic endometrial cancer that had continued to worsen after at least one prior systemic therapy.

Lenvatinib and pembrolizumab combination treatment showed an overall response rate (ORR) of 38.3%, with a partial response rate of 27.7% and a complete response rate of 10.6%. Patients were followed up for a median of 18.7 months. ORR is the percent of patients whose tumor is destroyed (complete) or reduced in size (partial) by a drug.

At data cut-off, the median duration of response was not reached, but had a range of 1.2 to 33.1 months, or longer. Sixty-nine percent of patients had a response lasting 6 months or longer.

Serious and possibly fatal side effects can occur with the use of lenvatinib and pembrolizumab for endometrial cancer. Immune-mediated reactions, infusion reactions, and other serious side effects can occur. Serious side effects occurred in over 50% of patients in studies, and 3% were fatal. There are also many common, but less serious side effects with this drug combination.

Speak with your doctor to understand the risk for side effects before treatment.

Learn more: Lenvatinib and pembrolizumab side effects (in more detail)

Bottom Line

• The combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) was approved by the FDA in September 2019 for the treatment of endometrial cancer.
• It is used to treat patients with advanced endometrial cancer that is not MMR deficient (dMMR) or MSI high (MSI-H) after at least one other drug treatment has been tried. You must not be eligible for curative surgery or radiation treatment.
• To find out if you have cancer that contains a biomarker for MSI-H/dMMR, a sample of tissue is taken and a test is ordered that will examine your tissue.

This is not all the information you need to know about lenvatinib and pembrolizumab for safe and effective use. Review the full drug product information at the above links and discuss this information, and any questions you have, with your doctor or other health care provider.