New Hope for Treating Advanced Endometrial Cancer
- There has been some exciting progress in treating advanced endometrial cancer in recent years, including a June 2024 approval of an immunotherapy drug called durvalumab (brand name Imfinzi) for certain patients with metastatic disease.
- The approval was based on results from the DUO-E study, which indicated that patients who received durvalumab with chemotherapy followed by maintenance durvalumab after chemotherapy had improved progression-free survival (PFS) compared to patients who only received chemotherapy.
- The research also found that the benefit of durvalumab was much larger in patients who had tumors that were categorized as mismatch repair deficient.
- Early evidence from the DUO-E trial also pointed to a possible additional benefit from adding olaparib, a drug known as a PARP inhibitor, for patients receiving durvalumab as compared to durvalamab without olaparib. These results are early, and the FDA has not yet approved olaparib in this setting.
- Combination therapy may be suitable for patients resistant to other drugs or with advanced metastatic endometrial cancer, providing new hope for those with limited treatment options.
The phase 3 DUO-E trial examined whether addition of an immunotherapy drug, durvalumab (brand name Imfinzi) improved outcomes when added to standard of care chemotherapy. As a secondary goal, the trial also examined whether addition of olaparib (brand name Lynparza), a PARP inhibitor, improved outcomes further when added to durvalumab + chemotherapy.
Read MoreWhat Did the Study Show?
The main finding in the DUO-E study was that patients who received durvalumab with chemotherapy followed by maintenance durvalumab after chemotherapy had improved progression-free survival (PFS) compared to patients who only received chemotherapy. PFS refers to the amount of time from trial enrollment until a patient’s cancer worsens.This benefit was seen both in patients who received durvalumab with olaparib and in those that received durvalumab without olaparib.
Importantly, the trial investigators planned ahead of time to see whether durvalumab was more effective in certain patients than others. It has been shown in numerous cancers that patients whose tumors have mutations (i.e. changes) in genes responsible for correcting mistakes occurring in DNA copying tend to respond better to immunotherapy, as these errors help the immunotherapy drugs to recognize cancer cells as abnormal.
This status is referred to as mismatch repair deficient, whereas tumors without these mutations are referred to as mismatch repair proficient.
The DUO-E trial investigators found that the benefit of durvalumab was much larger in patients with mismatch repair deficient tumors, and the FDA therefore has approved durvalumab only for these patients at this time.
This approval represents a significant advancement, offering new hope to women who historically had limited treatment options.
Early evidence from the DUO-E trial pointed to a possible additional benefit from adding olaparib for patients receiving durvalumab as compared to durvalamab without olaparib. These results are early, and the FDA has not yet approved olaparib in this setting.
“This may very well be practice changing.” Dr. Deanna Gerber, a gynecological oncologist at NYU Langone’s Perlmutter Cancer Center, told SurvivorNet.
“There are several recent studies that have shown a benefit of the addition of immunotherapy, such as IMFINZI, to chemotherapy. This is the first study to show a clinically meaningful benefit to immunotherapy plus a PARP inhibitor in the treatment of endometrial cancer,” Dr. Gerber added.
Promising Treatment Combinations
Combining treatments, whether it’s immunotherapy and chemotherapy or using two immunotherapies together, may be an option for certain patients with endometrial cancer.
This may include:
- Cases where a patient becomes resistant to other drugs
- Difficult cases of endometrial cancer that have advanced to the metastatic stage (spread to distant parts of the body)
In a long overdue development, a combination of durvalumab and and chemotherapy, with or without olaparib, can help delay disease progression for patients with advanced disease.
This multi-pronged approach targets cancer cells more effectively with drugs that each use different mechanisms of action, potentially improving patient outcomes in challenging scenarios.
“For a long time, patients with early stage endometrial cancer generally did very well with a combination of surgery, maybe some radiotherapy. However, there is 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,” Dr. Shannon Westin, a clinical investigator with the Department of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center, told SurvivorNet. Dr. Westin was also a lead author of the DUO-E study.
“Chemotherapy has been the standard of care for this patient population. And so the goal was to add new medications to chemotherapy, both with the chemo and following the chemo as a maintenance strategy, to try to improve outcomes for patients,” she added.
How Do Durvalumab and Olaparib Work?
Durvalumab is a type of immunotherapy called a human monoclonal antibody. It is a small molecule that binds to certain proteins on the surface of cancer cells. These include PD-1, PD-L1, and CD80 proteins that help cancer cells evade destruction by a patient’s native immune system.
More specifically, PD-1 and CD80 are proteins expressed on several immune cells. These proteins can interact with PD-L1, another protein expressed by tumor cells, essentially helping tumors hide from the immune system.
Durvalumab locates the hidden cancer cells and tells the immune system where to find them. It accomplishes that by latching onto the PD-L1 proteins and preventing them from interacting with PD-1 and CD80 proteins.
Olaparib belongs to a class of medication called poly-ADP ribose polymerase (PARP) inhibitors. These medications work by preventing cancer cells from repairing their damaged DNA, which eventually leads to their death.
The DUO-E trial showed that durvalamab plus olaparib and durvalamab alone both significantly improved the amount of time people can live without their cancer coming back in advanced endometrial cancer when added to chemotherapy.
The carefully designed study enrolled 718 patients in 253 locations across 22 countries including the US, South America, Europe, and Asia. All patients had newly diagnosed or recurrent advanced epithelial endometrial carcinoma (stages III or IV).
“The addition of both the durvalumab, which is an immunotherapy, and addition of the immunotherapy plus PARP inhibitor olaparib helped people live longer without their cancer coming back,” Dr. Westin says.
“And that’s progression-free survival. So we saw an improvement in progression-free survival in both groups, but importantly, the addition of the new drug, the PARP inhibitor, really seemed to enhance the benefit that we saw in the patient population.”
Dr. Gerber adds that the positive results are exciting “and really show promise for the treatment of advanced stage and metastatic endometrial cancer, which is universally considered difficult to treat. There has been a lot of momentum lately in the treatment of this group of patients.”
Dr. Ronald Natale explains how immunotherapy works to treat cancer.
Questions to Ask Your Doctor
If you have been diagnosed with advanced endometrial cancer, here are some questions you may consider asking your doctor to help understand your situation:
- What is the stage of my endometrial cancer?
- Would I benefit from immunotherapy and/or a PARP inhibitor?
- What benefits and side effects can I expect from treatment?
- Are there ways to manage the side effects of the treatment I receive?
- How much of my care will be covered by insurance and how much can I expect to pay out of pocket?
Learn more about SurvivorNet's rigorous medical review process.
