Major Progress in Advanced Endometrial Cancer Treatment
- New long‑term results from the RUBY clinical trial show that adding immunotherapy (dostarlimab) to chemotherapy may help some people with advanced or recurrent endometrial cancer stay in remission much longer than doctors have seen in the past.
- The biggest benefit was seen in patients whose tumors have a feature known as mismatch repair deficiency (dMMR) [when cancer cells can’t fix DNA damage properly], which is about 30% of those with endometrial cancer.
- Among patients with dMMR/MSI-H [a genetic biomarker known as Microsatellite Instability-High], in the trial, 57.9% had progression-free survival at four years with the dostarlimab + chemotherapy combination, compared to 15.7% in the placebo group.
- “We are talking about a cure in late‑stage disease for the first time,” Dr. Sarah Lynam, a gynecologic oncologist at University Hospitals/Seidman Cancer Center, tells SurvivorNet.
- While more follow‑up is needed, the findings suggest that immunotherapy may help the immune system keep cancer under control for years, offering new hope for patients who previously had few good options.
Researchers reported updated long-term results from the RUBY study, which evaluated the immunotherapy drug dostarlimab [brand name: Jemperli] in combination with chemotherapy for patients with advanced or recurrent endometrial cancer.
Read MoreThe greatest benefit was seen in patients whose tumors had a specific biological feature known as mismatch repair deficiency (dMMR). About one-third of endometrial cancers fall into this category. These tumors are often particularly responsive to immunotherapy because they are easier for the immune system to recognize and attack.
Mismatch repair deficiency (dMMR) is when cells can’t properly fix errors that happen as DNA is copied. Although this problem can contribute to cancer, it can also make tumors more likely to respond to immunotherapy, which helps the immune system find and attack cancer cells.
- About 2-3% of all early-stage solid tumors (like colorectal, gastric, or endometrial cancers) have this dMMR characteristic
- These tumors are often labeled “MSI-high” (microsatellite instability-high), which also signals a potential response to immune checkpoint inhibitors like dostarlimab
Lasting, Long-Term Benefits for Patients
The RUBY trial combined standard chemotherapy drugs with an immunotherapy that helps the body’s immune system find and destroy cancer cells, specifically dostarlimab plus carboplatin-paclitaxel [two chemo drugs often given together as a combination treatment, commonly called CarboTaxol].
Researchers used a statistical approach known as “cure modeling” to better understand what might happen to patients over many years. While the term can sound confusing, it does not mean researchers have proven that patients are cured.
RELATED: Treatment Option For Advanced Or Recurrent Endometrial Cancer
Instead, it helps estimate how many patients appear to reach a point where their risk of the cancer returning becomes very low and remains stable over time.
In the RUBY study, researchers found that more than half of patients with dMMR tumors may be experiencing this type of long-lasting benefit.
With a median of 4 years of follow-up:
- Progression-free survival (PFS) was seen in 57.9% of patients in the the dMMR/MSI-H population who received dostarlimab + chemotherapy.
- PFS was seen in just 15.7% in the placebo group.
- Survival curves, which track how patients do over time, appeared to level off after several years, meaning these patients continue doing well long after treatment has started.
This could represent a major shift in expectations.
In the past, advanced or recurrent endometrial cancer was generally viewed as a disease that would eventually progress despite treatment. The RUBY trial results suggest that some patients may now be entering years-long remissions that were previously uncommon.
“What’s most important in interpreting these findings is that we know that patients who have mismatch repair-deficient disease, which reflects about a third of patients with endometrial cancer, will really derive a lot of benefit from this treatment,” Dr. Lynam says.
“In patients where historically we had not been leveraging immunotherapy for endometrial cancer management, we are now saying that at two, three, four-plus year intervals, over half of patients may achieve a cure.”
The Power of Immunotherapy
Researchers believe immunotherapy may be helping the immune system develop a lasting memory of the cancer. Even after treatment is completed, the immune system may continue to monitor for cancer cells and prevent them from growing again.
While the findings are encouraging, experts stress that more follow-up is needed.
Understanding How Immunotherapy Works
Patients in the study will continue to be monitored, and researchers want to better understand how long these benefits will last. It is still too early to determine how many patients may ultimately remain cancer-free indefinitely.
Even so, the RUBY trial has already changed treatment for many patients with advanced endometrial cancer. It also highlights the importance of testing tumors for mismatch repair deficiency, since these patients appear to benefit the most from immunotherapy.
Just a few years ago, conversations about long-term remission in advanced endometrial cancer were rare. Today, thanks to studies like RUBY, doctors are beginning to have these discussions with some patients for the first time.
Although many questions remain, the latest results offer one of the strongest signs yet that immunotherapy may be fundamentally changing the outlook for women with endometrial cancer.
Expert Resources for Endometrial Cancer Patients
- Endometrial Cancer — Choosing The Right Doctor
- Endometrial Cancer — How to Spot the Signs And Symptoms Earlier
- Endometrial Cancer: Why The Patient’s Voice Needs To Be Part Of The Treatment Plan
- Advanced or Recurrent Endometrial Cancer Patients Have New Hopeful Combination Therapy Option
- Chemotherapy Can Play A Vital Role In Treating Advanced and Aggressive Endometrial Cancers
What To Know About Endometrial Cancer
After a woman has been diagnosed with endometrial cancer, the cancer is staged based on its spread within the body. A pelvic exam and imaging tests help determine if the cancer has spread or metastasized.
Some common risk factors for endometrial cancer include obesity, taking estrogen-only hormone replacement therapy after menopause, having never given birth or started menstruation at an early age, and having a family history of endometrial cancer.
Common symptoms associated with endometrial cancer include:
- Pelvic pain
- Pain during intercourse
- Unusual vaginal discharge
- Weight loss
- Urinary problems
WATCH: Different Types of Endometrial Cancer
Endometrial Cancer Treatment Options
Treatment options for endometrial cancer include surgery, radiation, chemotherapy, hormone therapy, and targeted therapy. Surgery is the most common treatment method.
“There are a lot of new exciting treatments for advanced endometrial cancer that we’ve just discovered over the last couple of years,” Dr. Dana Chase, gynecologic oncologist at UCLA Health, says.
“So even if you’re diagnosed with an advanced stage, ask your treating doctor what the latest treatments are, or even potentially, is there a clinical trial I can participate in for my endometrial cancer?”
Questions To Ask Your Doctor
- Have I been tested for mismatch repair deficiency?
- Is the dostarlimab plus chemotherapy combination an option for me?
- What potential side effects from immunotherapy should I be aware of?
- What are the options if my cancer does come back?
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