Kathleen N. Moore, MD
Ongoing clinical trials are in the midst of exploring the greater role of immunotherapy agents in patients with ovarian cancer who do not have microsatellite-instability high (MSI-H) tumors, according to Kathleen Moore, MD, who adds that such research could eventually determine the role of this class of drugs in the paradigm.
To date, immunotherapy has not had a defined role in ovarian cancer, outside of the 2% of patients with MSI-H disease. However, immunotherapy is currently being studied in combinations with VEGF inhibitors, PARP inhibitors, and other immunotherapy agents.
For example, preliminary findings of the phase I TOPACIO/KEYNOTE-162 trial demonstrated that the combination of niraparib (Zejula) and pembrolizumab (Keytruda) has early signs of efficacy in patients with platinum-resistant recurrent ovarian cancer or metastatic triple-negative breast cancer (TNBC). Out of 8 evaluable patients with ovarian cancer, 4 patients responded and the remainder had stable disease.
“Patients with BRCA mutations who respond to PARP inhibitors experience an increase in the neoantigen load, which makes bringing in an immune checkpoint inhibitor an efficacious option for these patients,” explains Moore.
In an interview with OncLive
at the 2018 Society of Gynecologic Oncology Annual Winter Meeting, Moore, assistant professor in the section of gynecologic oncology and director of the Oklahoma TSET Phase I Clinical Trials Program at Stephenson Cancer Center of the University of Oklahoma, discussed combination strategies with immunotherapy for patients with ovarian cancer.
OncLive: What is the current role of immunotherapy in ovarian cancer?
Moore: Immunotherapy is very exciting. There are not yet any indications in gynecologic cancers except for those who have MSI-H tumors, which we have seen in 2% of ovarian cancers but is more applicable to endometrial cancers. Currently, there is not an ovarian cancer indication for immunotherapy but there is ongoing clinical research.
Are there trials in development for immunotherapy in patients without MSI-H tumors?
For both endometrial and ovarian cancers, most patients do not have MSI-H tumors. The question is whether there is a role for immunotherapy in their care. I hope the answer is “yes.” There have been a few small trials of single-agent immunotherapy, mainly monoclonal antibodies targeting either PD-1 or PD-L1, but there are other checkpoint inhibitors that are under development. Currently, those studies have been done with PD-1/PD-L1 inhibitors across a number of agents.
The response rates have been from 11% to 25% across the studies, with some variants in eligibility. They are all within the same range. Those patients who responded in those studies tend to have durable responses, which is the ideal scenario. We want a patient's tumor to shrink but also gain that benefit for many months—not just 2 months.
We all agree that the signals are modest. Those patients were mostly unselected. One of the studies tried to select for PD-L1 expression on the tumor, but it did not seem to identify a group of patients who did better than unselected patients.
There is a signal. It is most likely that the efficacy for this class of agents in ovarian cancer without MSI-H tumors will be in combinations.
What is the rationale behind combinations of immunotherapy and VEGF inhibitors?
There is a lot of basic science and translational science that supports these combinations. It is good that we are following the science in developing these combinations, rather than just adding things together and hoping they work.
There are several combinations that are of interest across all solid tumors, including ovarian cancer. Those include combinations of immune agents with antiangiogenic agents, combinations of immune agents with PARP inhibition or other DNA-damaged response inhibitors, combinations with cytotoxic chemotherapy, and combinations with other immune agents. Trying to capitalize on different aspects of our immune system is the rationale behind immunotherapy combinations.