Study: Managing the side effects of advanced endometrial cancer treatment

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

Relevance Rating Details

What is this study about?

This study looked more closely at the side effects of the targeted therapy Lenvima (lenvatinib) plus the immunotherapy Keytruda (pembrolizumab) when used to treat advanced endometrial cancer that has progressed or returned after prior treatment and has some specific markers on tumor profiling. The study authors discussed the most common side effects and how to manage them.

Why is this study important?

In 2021, the FDA approved Lenvima plus Keytruda for advanced endometrial cancer. This treatment is an option for many people with endometrial cancer that has already been treated with chemotherapy.

This approval was based on a trial that showed that the combination of Keytruda and Lenvima is more effective than chemotherapy for advanced endometrial cancer. The trial showed that people who received the combination therapy lived longer and had more time without cancer growth or spread. The study reviewed in this report provides more information on the side effects of Lenvima plus Keytruda and how they can be managed.

The results of this study can help patients and their healthcare providers better understand these side effects. Knowing what to look for and how to manage these effects can help to ensure that patients benefit as much as possible from the therapy.

Study findings

Lenvima is a daily pill and Keytruda is an injection given into the vein every three weeks. Currently, Lenvima plus Keytruda may be used to treat people with advanced endometrial cancer:

• who have already tried a drug therapy (likely chemotherapy) that did not work or is no longer working.
• who are not able to have surgery or radiation.
• whose tumors do not have microsatellite instability.
  • Tumors that do not have microsatellite instability are called pMMR (or MMR-P) or MSI-Low
  • People with Lynch Syndrome often have tumors that are MSI-high/dMMR and are not included in this group.

Lenvima and Keytruda work in different ways and have different possible side effects. People usually experience side effects within three months of starting these drugs.

This study looked more closely at the side effects experienced by people in the clinical trial that led to FDA approval. Results are based on the experiences of 406 people in the clinical trial who stayed on the drugs for an average of 231 days.

Side Effects

The most common side effects of lenvatinib plus pembrolizumab; cancer grade and time until onset are listed below.

*Musculoskeletal disorders are conditions that affect bones, joints, muscles and connective tissues (e.g., tendonitis).

**Stomatitis presents as ulcers that can cause pain and difficulty drinking and eating.

***Hand-foot syndrome is also known as palmar-plantar erythrodysesthesia (PPES). It usually affects the palms of the hands and soles of the feet, causing redness, pain or discomfort in these areas.                             

More than half of the participants in the clinical trial developed high blood pressure, fatigue, musculoskeletal disorders, diarrhea or hypothyroidism.

Side effects that occurred shortly after beginning treatment included high blood pressure, fatigue and musculoskeletal disorders.  Side effects that occurred later included hypothyroidism, PPES and weight loss.

Both targeted therapy and immunotherapy have known side effects, some of which can be serious.  You can learn more about the side effects of targeted therapy here and the side effects of immunotherapy here.

Management of side effects

This study also looked at specific side effects and how to deal with them. In general, the following strategies helped:

• Healthcare providers and patients learned about possible side effects before treatment begins.
• Patients watched closely for signs of side effects and notified doctors right away of any issues.
• Took steps to prevent side effects when possible.
• Prevented and treated side effects with medicine when possible (i.e., for nausea, vomiting, diarrhea, hypothyroid and high blood pressure).
• Monitored side effects for improvement.
• Identified which drug was causing the side effect, often by paying attention to the time when the drug was taken.
• Paused one drug at a time when recommended by a doctor (usually paused Lenvima as a first step).
• Reduced the dose of Lenvima when recommended by a doctor (lowering the dose of Keytruda is not recommended).

What does this mean for me?

If you have advanced recurrent endometrial cancer, ask your doctor if Lenvima plus Keytruda is an option for you.

If you are already taking or will begin taking this drug combination, share this article with your doctor and discuss the possible side effects.  You and your healthcare providers can work together to watch closely for side effects and then manage them when they occur, modifying drug doses if needed.

Learning how to prevent and manage the serious side effects of these drugs can help you stay on the treatment longer, which may lead to better outcomes.

Even if you are not eligible for this drug combination, you may be eligible for other targeted or immunotherapy treatment options.  Learn more about targeted and immunotherapies for endometrial cancer here.

You may also want to talk to your healthcare providers about other treatment options, including clinical trials.

Reference

Colombo N, Lorusso D, Monk BJ, et al. Characterization and management of adverse reactions in patients with advanced endometrial cancer receiving lenvatinib plus pembrolizumab. The Oncologist. 2024; 29:25-35.

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 9/25/24