Carboplatin and Pembrolizumab to Prevent Progression After Serological Detection of Recurrence in Ovarian Cancer
Abstract
Treatments for recurrent ovarian cancer are much less effective than ones available when the disease is first diagnosed. These chemotherapies often have more severe side effects, and they are not able to cure the cancer. Patients faced with recurrences of their ovarian cancer are the ones that most urgently need newer, more effective therapies with fewer side effects. Therapies that harness a patient’s own immune system to attack a cancer have become available for many cancers. Pembrolizumab is one such drug. It has been tested in patients with ovarian cancer, but only a small fraction of those patients have seen their tumor shrink. A couple of discoveries have changed how we think about how this drug may be used best in ovarian cancer. First, although chemotherapies have long been known to suppress a patient’s immune system in potentially dangerous ways, we have also learned that some chemotherapies can also have certain beneficial effects on the immune system. Carboplatin, one of the most commonly used in the treatment of ovarian cancer, has been shown to stimulate immune cells through the same pathway as pembrolizumab. Second, pembrolizumab has been shown to be most successful in other cancers when it is given in patients with smaller tumors who also have with more active immune cells in their circulation. Therefore, combining carboplatin with pembrolizumab may be able to increase its effectiveness. There is a scenario in the natural course of ovarian cancer that is well suited to using this strategy. Ovarian cancer patients who have been treated to a remission with traditional surgery and chemotherapy will often be monitored closely for a recurrence with CA-125 blood testing because it is known that there is often a high risk for the disease to return. This test has the ability to detect a recurrence very early, before a scan can detect it, or even before a patient has any symptoms. In this situation, the standard treatments are usually hormonal therapies that often only briefly delay recurrences; therefore, some doctors will advise patients to wait to be treated because it isn’t clear whether starting treatment early will help patients live longer. This situation is understandably very stressful for patients and frustrating for their doctors. But this may be just the situation where this form of immune therapy may work the best. Unfortunately, these patients are often not allowed to enroll in clinical trials because the rules for participating in many clinical trials will often require that tumors be visible on a scan. We are proposing a clinical trial to treat patients with early ovarian cancer recurrences detected by CA-125 and not seen on scans with pembrolizumab every 3 weeks after they receive a single dose of carboplatin. We will treat 22 patients and compare what fraction of patients then develop tumors that can be measured on a scan to what we have seen in patients treated with hormonal therapies in the same situation. We will also test the tumor and immune cells in each patient’s blood for levels of proteins that are related to how we think these two drugs work together and use that to try to predict which patients respond best to this treatment. The results from this project will help identify a way to use immune therapy effectively in patients with ovarian cancer. It seeks to find a way to preserve a patient’s quality of life for as long as possible by starting treatment when they are feeling well with a therapy with fewer side effects than chemotherapy and keeping their disease at bay for as possible. It also tries to identify whether there are indicators in the tumor itself or in the patient’s blood that can predict which patients might respond to this approach. This can then produce a test that will identify which patients this treatment would work best for and prevent other patients from undergoing a treatment that will not benefit them.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910009
Entities
People
- John Liao
Organizations
- United States Army
- University of Washington