Dr. Ravi Madan, the clinical director of the National Cancer Institute’s Genitourinary Malignancies Branch, focuses on immune-stimulating therapies. In particular, he’s interested in how we can combine these approaches with other therapies to improve patients’ lives.
Prostatepedia spoke with him about which immunotherapy combinations he feels are the most promising.
(Members can read the conversation in their January issue.)
What kinds of immunotherapy are available now and what is still emerging?
Dr. Madan: There is an FDA-approved therapeutic cancer vaccine called Provenge (sipuleucel-T) that is available in the United States, Europe, and some other parts of the world.
Provenge (sipuleucel-T) is a therapeutic cancer vaccine derived from a patient’s own immune cells. These immune cells are removed from a patient and then exposed to a target protein. Those immune cells are then reinfused back into the patient after that immune-activation phase. The goal is that those activated immune cells will seek out and destroy prostate cancer cells; this has been shown to increase survival in men with advanced prostate cancer, or what we call metastatic, castration-resistant prostate cancer.
Another strategy that is more common throughout the broader medical oncology field is something called immune checkpoint inhibitors. These are approved for and have demonstrated efficacy in many cancers. They help limit regulatory mechanisms that have the potential to turn off immune cells. Sometimes the cancer cells themselves are the ones turning off the immune cells that are trying to recognize and kill them.
On their own, unfortunately these agents have not proven efficacious in prostate cancer. However, several combinations, including some combinations with vaccines, have demonstrated some preliminary evidence of a greater impact than when we just use immune checkpoint inhibitors alone. Several of these combination studies will be very interesting to watch in the near future.
Which combinations do you think appear most promising?
Dr. Madan: There are multiple strategies of interest, but one strategy combines a vaccine with immune checkpoint inhibitors. Our group at the National Cancer Institute, as well as one at the University of Wisconsin, has demonstrated some preliminary evidence that this combination may have an impact. There is also ongoing research looking at combining Xtandi (enzalutamide) with an immune checkpoint inhibitor. In preliminary data, that combination seems to have an impact in a subset of patients.
Why aren’t you looking at Zytiga (abiraterone)? Is there something specific about Xtandi (enzalutamide) that makes it a better combination partner?
Dr. Madan: I’m not aware of any specific studies looking at a combination of Zytiga (abiraterone) and a checkpoint inhibitor, though I wouldn’t be surprised if there are some going on. There is some clinical data that suggests that after treatment with Xtandi (enzalutamide), immune cells may have a higher expression of PD-1, which may create a stronger rationale for the Xtandi (enzalutamide) combination.
In addition to the vaccine combinations, there is a strong rationale to combine immunotherapies with other antiandrogen therapies, including standard androgen deprivation therapy as well as forms of radiation, including definitive radiation.
There are also multiple trials combining immunotherapy with chemotherapy.