Gynecological clear cell cancers (CCCs), very aggressive forms of ovarian and endometrial malignancies, respond poorly to chemotherapy. The low response rates underscore a significant clinical need to develop novel approaches to treat these diseases.
A new study published in JAMA Oncology reports on the efficacy of a combination therapeutic approach using two immune checkpoint inhibitors (ICIs): nivolumab and ipilimumab. ICIs block proteins called checkpoints that are upregulated on immune cells. Checkpoints regulate the immune system, preventing it from responding to our own cells and tissues, but this can prevent the immune system from activating in response to foreign antigens that cause diseases like cancer. ICIs block checkpoints, thus preventing the breaks that keep the immune response from becoming too strong and improving anti-tumor responses.
Two ICIs approved by the U.S. Food and Drug Administration (FDA) block checkpoints called programmed cell death 1 protein (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4). Oncologists can prescribe these drugs, referred to as PD-1 and CTLA4 blockers, in combination with each other or with other treatments, such as surgery or chemotherapy. To study new treatment possibilities for gynecological CCCs, a team of researchers set out to evaluate the efficacy of combination PD-1 and CTLA-4 blockade.
The researchers established a multicenter phase 2 clinical trial enrolling patients with advanced clear cell ovarian cancer (CCOC) or clear cell endometrial cancer (CCEC). The study included 28 women with an average age of 55 years. Of the women enrolled, most (24) had CCOC, and 19% had received a prior course of therapy. The majority of the patients were in advanced stages of the disease, with some having undergone previous treatments that were unsuccessful.
Patients received four doses of PD-1 blocker nivolumab combined with CTLA-4 blocker ipilimumab every three weeks. They continued to receive nivolumab alone monthly for up to 96 weeks, or until their disease progressed or they experienced unmanageable side effects.
The researchers evaluated the overall objective response rate (ORR), a measure of how many patients experience a partial or complete response to treatment. The results were reassuring, with just over half of the participants showing a response (54%). Three patients achieved a complete response, indicating no sign of malignancy after treatment, while 12 patients experienced a partial response, where the patient’s cancer burden decreased, but remained detectable. The study also looked at progression-free survival (PFS), a measure of how long a patient lives with their disease while it remains stable and does not progress, or get worse. The analysis showed that 58% of patients achieved PFS six months following the start of treatment.
The encouraging results of this clinical trial demonstrate that the combination of PD-1 and CTLA-4 blockade has the potential to greatly benefit patients advanced gynecological CCCs. Because of the high demand for new treatment options for patients with these aggressive malignancies, this phase two trial presents adequate and encouraging data supportive of initiating further investigation of this ICI combination approach.
Sources: JAMA Oncol, Int J Gynecol Cancer, Int J Gynecol Cancer