Combination Immunotherapy Emerges as a New Treatment Option for Rare Gynecological Cancers

A new combination of agents classified as "immune checkpoint inhibitors", the new-generation immunotherapies known as ipilimumab and nivolumab, may offer an opportunity for good results in the treatment of patients with rare gynecological cancers, according to a study to be presented at the ASCO 2020 Virtual Congress.

Gynecological cancers (cancers specific to women and the female reproductive tract) usually bring to mind the conventional uterine, cervical (cervix of the uterus) and ovarian (ovary) cancers. This study included the following rare subtypes of gynecological cancers:

Rare cancers are unfortunately an area of slow progress in oncology when it comes to developing new drugs, and there is a major unmet medical need in their treatment. However, rare types of gynecological cancers account for a substantial proportion of these cancers, around 55-60%, so we need to find new treatments for these patients.

Immunotherapies—especially immune checkpoint inhibitors—have become a new cancer treatment option by activating the immune system against cancer to eliminate or control tumors. For example, the PD-1 blocker nivolumab combined with the CTLA-4 inhibitor ipilimumab is effective for patients with advanced melanoma, kidney or lung cancer. However, few studies to date have examined the value of this combination in rare gynecological cancers.

A Phase-II Study Evaluating Combination Immunotherapy in Rare Gynecological Cancers

A total of 41 patients with rare gynecological tumors were enrolled in this phase II clinical trial and received 3 mg/kg nivolumab and 1 mg/kg ipilimumab every 3 weeks for the first 4 doses, followed by 3 mg/kg nivolumab every 2 weeks until progression (disease advancement). The primary endpoint was the clinical benefit rate (complete response plus partial response plus stable disease), and secondary endpoints included whether efficacy was associated with specific predictive biomarkers (e.g., PD-L1, tumor mutational burden).

Study Results

• Of the 41 patients, 39 had previously received at least one line of another treatment.
• Objective responses were observed in 11 patients (27%) and stable disease in another 9 patients, giving a clinical benefit rate of 49%.
• Almost two-thirds of patients (63%) experienced an immune-related adverse event, but the adverse-event profile was similar to that seen in kidney and colorectal cancers treated with this combination.

If the findings of this phase-II study are confirmed in a further phase-III clinical trial with randomized patient selection, they will give oncologists a new tool to consider when choosing treatment for patients with rare gynecological tumors, especially young women.

Klein and colleagues reported that they next planned to conduct a randomized study in a larger sample of patients with many types of rare cancer, not only those of gynecological origin, to confirm the findings in this group.