The randomized clinical trial will compare whether the addition of a monoclonal antibody called pembrolizumab — a form of immunotherapy — to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer recurrence in patients with newly diagnosed stage I-II endometrial cancer characterized by mismatch repair-deficient (dMMR) tumors.
The national principal investigator for this trial, which is sponsored by the National Cancer Institute (NCI) in collaboration with NRG Oncology, is Floor Backes, MD, associate professor in the Division of Gynecologic Oncology at Ohio State and member of the Cancer Control Program at the OSUCCC – James. Patient accrual is under way with an anticipated enrollment of 168.
Backes says immunotherapy with monoclonal antibodies such as pembrolizumab may help the body’s immune system attack the cancer and interfere with the ability of tumor cells to grow and spread, while radiation therapy uses X-rays to kill tumor cells and shrink tumors. The primary objective of this study, she adds, is to compare the three-year recurrence-free survival of women with high intermediate-risk stage I/II dMMR endometrial cancer who are treated with radiation and pembrolizumab versus those who are treated with radiation alone.
“Patients with early-stage endometrial cancer and a certain change in their tumor, called a mismatch repair deficiency or microsatellite instability (MSIhigh), have a higher risk of cancer coming back,” Backes says, explaining that MSI is a condition that predisposes to gene mutations and signifies that DNA mismatch repair is not functioning properly (deficient).
“These tumors appear less sensitive to chemotherapy but more sensitive to immunotherapy,” she says. “This trial specifically enrolls this select population of endometrial cancer patients for personalized therapy involving targeted immunotherapy plus radiation, or just radiation.”
She says the trial is “the first of its kind in randomizing a very specific population of patients for receiving targeted therapy. It will show whether this approach will change the standard of care and result in better outcomes and survival for these patients."