Endometrial cancer is the most common form of cancer that develops in the uterus, and there is currently a need for more treatment options, especially when it comes to the advanced or recurrent form of the disease. Luckily, a new study – the DUO-E trial – is investigating maintenance durvalumab when used with platinum-based chemotherapy maintenance durvalumab, both with and without olaparib. Targeted Oncology recently interviewed Shannon N. Westin, MD, MPH, FACOG, of the University of Texas MD Anderson Cancer Center about this trial and its importance.
About Endometrial Cancer
First, it’s necessary to understand what exactly endometrial cancer is. It is the most common form of cancer that forms in the uterus. Specifically, it begins to develop in the uterine lining. Medical professionals are unsure as to why this happens, but they have identified a number of risk factors: never being pregnant, later menopause, earlier menstruation, older age, obesity, changes in female hormones, hormone therapy administered for breast cancer, and an inherited colon cancer syndrome.
Regardless of cause or risk factors, symptoms of this cancer include vaginal bleeding in between periods, pelvic pain, and vaginal bleeding that occurs after menopause. Treatment for this cancer typically means removing the Fallopian tubes, uterus, and ovaries. If this cannot occur, other treatment options include chemotherapy, targeted drug therapy, radiation, immunotherapy, hormone therapy, and supportive care.
About the DUO-E Trial
This Phase 3 trial is randomized, placebo-controlled, double-blind, and multicenter in an effort to investigate the efficacy and safety of durvalumab when used in combination with platinum-based chemotherapy maintenance durvalumab both with and without olaparib. Participants are adult females who have been diagnosed with epithelial endometrial carcinoma, recurrent endometrial cancer, or newly diagnosed stage III or IV endometrial cancer.
In terms of endpoints, the primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), overall survival (OS), second progression, and duration of response, among others. Safety will be evaluated based on adverse events defined by the National Cancer Institute criteria.
Interview with Shannon N. Westin
Shannon first spoke of the importance of the DUO-E trial for this patient population, as there is a need for a new standard of care. The current treatment consists of a combination chemotherapy regimen of paclitaxel and carboplatin, which we know does not necessarily cure patients, especially those with advanced or recurrent cancer. Considering that a large number of patients are not diagnosed in the early stages, this trial and new treatment options are necessary.
In fact, Westin touched upon unmet needs for those with recurring cancer. The goal of treatment is to prevent a recurrence, as this disease is very difficult to cure after one. So while those with advanced endometrial cancer need more treatment options, this area is one with “a lot of opportunities to improve outcomes.”
Durvalumab for Endometrial Cancer
When it comes to durvalumab, Westin also explained the historical rationalization for using this treatment. She stated that a combination of chemotherapy and immunotherapy holds opportunities for synergy, as chemotherapy works to eradicate the cancer while immunotherapy stimulates the immune system to prevent recurrence.
In fact, prior research has pointed to checkpoint inhibitors based on the prevalence of microsatellite instability; 30% of patients have a tumor with this abnormality. Additionally, PARP inhibitors, one of which is olaparib, have shown activity in other cancers that typically impact females, such as breast and ovarian cancer. Due to the high levels of homologous recombination deficiency, at least 50% of endometrial cancer patients could stand to benefit from the addition of a PARP inhibitor like olaparib.
Study Design
There are three arms within this study. The first group receives solely chemotherapy with a placebo maintenance therapy, the second receives durvalumab with durvalumab maintenance and a placebo, and the final group receives both chemotherapy and maintenance durvalumab in addition to olaparib.
Overall, 699 patients will enroll and be evaluated in regard to PFS. This group of participants is special due to the high risk they face with endometrial cancer. Additionally, this study allows patients with recurrent cancer who have received past treatment with chemotherapy to be evaluated as well. As enrollment is currently running smoothly, medical professionals hope to start seeing results within the next few years.
Looking Forward
Beyond the importance of this study that has already been discussed, Westin also pointed out the patient-reported outcomes that will be investigated. As this trial is investigating maintenance therapy and treatment for recurrent cancer, quality of life is extremely integral and must be considered.
Hopefully, this trial leads to another treatment option for endometrial cancer patients.
