Study: Managing the side effects of advanced endometrial cancer treatment
Immunotherapy plus targeted therapy is a treatment option for advanced endometrial cancer that has progressed after prior treatment. People who start the two-drug combination are more likely to have a positive experience if they learn about the possible side effects and when they might occur. The most common side effects and how to manage them are discussed in this review. (Posted 9/25/24)
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RELEVANCE
Most relevant for: People with advanced endometrial cancer.
Relevance: Medium-High
Strength of Science: Medium-High
Research Timeline: Post Approval
What is this study about?
This study looked more closely at the side effects of the Lenvima (lenvatinib) plus the 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 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 .
- Tumors that do not have microsatellite instability are called pMMR (or MMR-P) or MSI-Low
- People with 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.
| Side effect | % any grade | % grades 3-4 | Weeks to first onset |
| High blood pressure (hypertension) | 65% | 38% | 2.1 |
| Fatigue | 59% | 11% | 2.3 |
| Musculoskeletal disorders* | 53% | 5% | 3.1 |
| Inflammation of the mucous membranes in the mouth (stomatitis)** | 36% | 3% | 4.3 |
| Nausea | 50% | 3% | 4.7 |
| Decreased appetite | 45% | 8% | 4.9 |
| Protein in the urine (proteinuria) | 30% | 5% | 4.9 |
| Vomiting | 37% | 3% | 7.6 |
| Diarrhea | 54% | 8% | 7.9 |
| Underactive thyroid (hypothyroidism) | 69% | 1% | 8.7 |
| Hand-foot syndrome *** | 22% | 3% | 9.7 |
| Weight loss | 34% | 10% | 10.7 |
*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).
