How is Immunotherapy Used for Advanced or Recurrent Endometrial Cancer?

Mismatch repair-deficiency (dMMR) refers to a condition where the body’s natural system for correcting errors in DNA replication is impaired, leading to increased mutations and a higher risk of developing certain types of cancer.

MSI is a genetic marker characterized by changes in the length of microsatellites (short, repeated sequences of DNA) due to errors in the DNA mismatch repair system. Essentially, tumors with high levels of MSI (MSI-H) accumulate numerous mutations, making them more recognizable to the immune system.

New Hope for Advanced Endometrial Cancer

New data suggests that dostarlimab-gxly (Jemperli) plus regular chemotherapy (carboplatin/paclitaxel), can be very effective for the treatment of patients with primary advanced or recurrent endometrial cancer, regardless of their mismatch repair status.

Dostarlimab-gxly was already approved for metastatic (cancer that has spread) and recurrent (cancer that has come back) endometrial cancer in cases where chemotherapy did not work.

“There’s a population of patients that are diagnosed at a later stage, stage three or four, or that have their cancer come back after initial therapy. And those patients have had a really hard time,” says Dr. Shannon Westin, a professor in the department of gynecologic oncology and reproductive medicine at the University of Texas, MD Anderson Cancer Center in Houston, Texas.

According to Westin, the latest treatments combining immunotherapy with standard chemotherapy plus a drug that prevents cancer cells from fixing their own DNA are showing promise.

The results are encouraging, especially for patients who have late-stage endometrial cancer or their disease has come back. And this new data shows that there is benefit regardless of the patient’s genetic mutation.

What Did the Research Show?

The research demonstrated a 31% improvement in overall survival compared with chemotherapy alone in patients with primary advanced or recurrent endometrial cancer.

The results showed that the median overall survival for patients who received both dostarlimab-gxly and chemotherapy was 44.6 months, compared to 28.2 months for patients who were treated with just chemotherapy.

“These data confirm dostarlimab plus carboplatin/paclitaxel is a new standard of care for patients with primary advanced or recurrent endometrial cancer, regardless of their mismatch repair status,” said Dr Matthew Powell, Chief in the Division of Gynecologic Oncology at Washington University in St. Louis, in an oral presentation during the meeting.

What is Immunotherapy?

Immunotherapy uses a person’s own immune system to fight the cancer. It’s being hailed as the new frontier in cancer treatment. These therapies focus not just on attacking cancer broadly but on finding and attacking the cancer’s specific weaknesses.

Immunotherapies — like durvalumab — train the immune system to spot and destroy cancer cells more efficiently. Dr. Westin emphasizes the significance of this shift.

“We’re not just treating cancer, we’re outsmarting it by targeting its vulnerabilities. This approach marks a significant departure from one-size-fits-all treatments, offering a beacon of hope for those with advanced stages of endometrial cancer,” she says.

While immunotherapy drugs are gaining more popularity, it’s important to know that, as with any drug, they can come with side effects.

Side Effects

Like all cancer treatments, these therapies can also have side effects. The decision to use these treatments involves weighing the potential benefits against the risks and side effects, tailored to each patient’s situation and health condition.

Some of the more common side effects of this treatment include:

• Gastrointestinal issues such as nausea, vomiting, abdominal pain or diarrhea
• Fatigue (feeling tired)
• Anemia (low red blood cells)
• Rash
• Respiratory symptoms such as cough, shortness of breath or chest pain

Other Immunotherapy Drugs to Consider

Two additional drugs, pembrolizumab (Keytruda) and atezolizumab (Tecentriq), share a common goal with dostarlimab (Jemperli): to empower the immune system to more effectively fight cancer.

While each targets different mechanisms within the immune escape pathway, they collectively represent important tools in the management of various cancers, especially in recurrent cases where traditional therapies may have failed.

Pembrolizumab is a widely used treatment for recurrent cancer. It is a type of immunotherapy known as a checkpoint inhibitor. It works by targeting a protein on the immune system’s cells called PD-1.

Normally, this protein helps keep the body’s immune responses in check, but cancer can exploit this mechanism to avoid being attacked by the immune system. By blocking PD-1, pembrolizumab helps boost the immune system’s ability to fight cancer cells. It’s often used for treating cancers such as melanoma, lung cancer, and head and neck cancers, among others.

Atezolizumab, another checkpoint inhibitor, functions similarly but targets a different protein called PD-L1, which is found on the surface of some cancer cells. When PD-L1 binds to PD-1, it tells immune cells not to attack.

By inhibiting PD-L1, atezolizumab helps restore the immune system’s ability to detect and destroy cancer cells. This drug is commonly used in the treatment of bladder cancer and non-small cell lung cancer.

Questions to Ask Your Doctor

• Is this dostarlimab-gxly (Jemperli) or another immunotherapy drug a good choice for me?
• What improvements can I expect, and how will we track progress?
• What side effects can I expect, and how can we deal with them?
• How will these treatments affect my daily routine and well-being?
• What is the cost, and is there financial assistance available?

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