Then, one study suggested that there was some activity in women who have tumors without any defects when given in the maintenance setting. That effect was much more modest than for tumors in women who do have defects for DNA repair.
What types of ongoing trials in this space are geared toward your discussion?
We have a number of trials that [range from] testing standard agents, such as PARP inhibitors and angiogenesis inhibitors, to more interesting and sophisticated trials that take antibodies and combine them to antibody-drug conjugates, or test immunotherapy in ovarian cancer and endometrial cancers.
We have a number of trials that are really testing targeted inhibitors; we have a very exciting folate receptor trial in recurrent ovarian cancer, because ovarian cancers do express the folate receptor and there is some thought that even endometrial cancers might express the folate receptor. There is some discussion about developing a trial for the folate receptor antibody in endometrial cancer.
Other trials that are exciting in ovarian cancer include the combination of a PARP inhibitor and angiogenesis inhibitors. Cediranib and olaparib is one combination, and there are other combination therapies with PARP inhibitors.
Combining PARP inhibitors with other agents to treat women who do not have BRCA
mutations is a very exciting area, because we know the PARP inhibitors work best in women who carry BRCA
mutations either inherited or within the tumor, and also work well in women with defects in DNA repair. How to combine them with agents to apply them to the rest of the population is something that we’re actively studying because, after all, 50% or less of women will be in those categories that I mentioned.
Another exciting area is the microsatellite-instability (MSI)-high/positive endometrial cancers. MSI positivity accounts for about 35% of endometrioid endometrial cancers or about 20% of overall endometrial cancers. Now, a few months ago, checkpoint blockade with pembrolizumab (Keytruda) was approved for use in MSI-high/positive tumors. Obviously, it is very exciting because it is approved for a molecular indication that would include endometrial cancers, colorectal cancers, gastric cancers, and really any cancer that happens to have MSI-positivity or be an microsatellite unstable disease.
The exciting part about immunotherapy is that it really capitalizes what we already knew about the endometrial cancers and, of course, some MSI-high tumors are actually inherited through a defect in mismatch-repair (MMR) genes, so that is also important for genetic screening and genetic counseling. We have another link between inherited genetic events that are now tangentially leading to actually very effective treatments. Therefore, we have the inherited BRCA mutations that put people at risk for ovarian cancer and are now a therapeutic target with PARP inhibitors.
Now, we have the MMR genes, which can put you at inherited risk for colorectal cancer and endometrial cancer, and now the therapeutic target with checkpoint blockade, so these are very exciting and gratifying solutions for years of research.
You co-chaired this State of the Science SummitTM. What is the value in community physicians attending a more intimate event like this?
This State of the Science Summit on ovarian cancer was really designed to share the latest in various aspects of ovarian cancer research and treatment with the community, and the regional area here. We wanted to talk about the research going on in the lab, prevention, screening, early detection, primary treatment, recurrent treatment, and novel therapeutics, such as immunotherapy and PARP inhibitors, and that is what was featured prominently in this event.
Liu J, Barry WT, Birrer M, et al. Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer. J Clin Oncol. 2017;35 (suppl; abstr 5535).