Dmitriy Zamarin, MD, PhD
Immunotherapy with PD-1/PD-L1 inhibitors has been slower to develop in gynecologic cancers than in several other solid tumors.
Success with these agents in gynecologic cancers will require combination approaches, biomarker development, and identifying subpopulations who more likely to benefit, such as patients with microsatellite instability-high tumors, explains Dmitriy Zamarin, MD, PhD.
In an interview with OncLive,
Zamarin, a medical oncologist at Memorial Sloan Kettering Cancer Center who specializes in the care of women with gynecologic cancers, discusses previous findings and the next steps necessary to advance immunotherapy in the field.
Onclive: What have been the findings so far with immunotherapy in gynecologic cancer?
The immune checkpoint inhibitors, which have been the most promising in other cancers, have unfortunately not worked out as well in gynecologic malignancies. In the general population now of cervical cancer, ovarian cancer, or endometrial cancer, the preliminary reports that have been presented at meetings show the response rates seem to range from 10% to 15%.
It may also be another 10% to 15% of patients having disease stabilization, which is much lower than what has been seen in some other cancers like bladder cancer, lung cancer, and myeloma. These drugs are certainly very promising for the patients with gynecologic cancers, but I think we still need to identify the right kind of patients that could benefit from these drugs, and unfortunately, we don't have the right biomarkers yet.
The one exception to this is the use of the PD-1 inhibitors in patients with mismatch repair deficiency, such as endometrial cancer that is associated with Lynch syndrome. Even though there are only a few patients that have been reported who were treated with these drugs, their response rates are high, so far.
In a paper that was published in The New England Journal of Medicine
last year, it was discussed that many of the patients that had high microsatellite instability-high cancers, including colorectal and endometrial cancers, seemed to have responded very well. I think that these drugs are certainly providing a lot of promise within this minor population.
For the rest of the patients, I think these drugs still hold promise and the response rate does mirror something that we see with single-agent chemotherapies in the later line settings, but it's not going to be the immunotherapeutic solution to gynecologic cancers.
Can you discuss the current state of biomarker development in gynecologic cancers?
This is a problem that plagues not just gynecologic cancers but any cancer. Unlike the biomarkers for some of the targeted therapies, where presence of a specific mutation or overexpression of a certain protein can predict whether a patient would respond to certain drugs or not, I think we are understanding that the biomarkers for immunotherapies are likely going to be much more complex.