Julie Graff, MD
Although modern immunotherapy has yet to have a breakthrough in prostate cancer to the degree it has had in lung cancer or urothelial carcinoma, combinations with anti–PD-1/PD-L1 agents are beginning to show promise for these patients in clinical trials.
, Julie Graff, MD, an assistant professor of medicine at OHSU Knight Cancer Institute, commented on the state of immunotherapy in mCRPC and some of this ongoing research.
OncLive: Can you discuss your lecture on immunotherapy in prostate cancer?
I spoke about the status of immunotherapy in prostate cancer, which is a very interesting topic that is evolving. We have 1 approved immunotherapeutic agent called sipuleucel-T in mCRPC, which is a cellular vaccine. There are several other vaccines in development. We also have studies involving checkpoint inhibition, as well as chimeric antigen receptor (CAR) T-cell therapy in prostate cancer.
What is the status of immunotherapy currently, and what do you foresee in the next 5 to 10 years in this disease?
Sipuleucel-T is pretty well tolerated. Essentially, we take out the patient's blood and send the white blood cells to a factory where they are exposed to a prostate-specific antigen and growth factors and are put back into the patient, so there are not a lot of toxicities. Some patients have some itching, so we give Benadryl, or [they might have a] slight fever. The problem is prescribing [sipuleucel-T] when patients have prostate cancer–related symptoms because it does not really shrink down tumors. Anyone with rapidly growing tumors should not get this therapy because it will not work for them in time.
We will know [soon] whether checkpoint inhibitors will work in prostate cancer, [which will] probably be in combination with other agents. We will also know whether CAR T-cell therapies work, and the vaccines that are under development—viral and DNA vaccines—should have mature data. However, I do expect that we will have more immunotherapy at that time than just the sipuleucel-T.
Please expand on the potential for checkpoint inhibitors in prostate cancer.
I do see potential for CTLA-4, PD-1, and PD-L1 to move into prostate cancer. I will tell you, though, that there are 2 negative studies of ipilimumab (Yervoy). Therefore, that one may not move forward unless someone combines it with another therapy or we molecularly test patients to see who is appropriate for that therapy. There are multiple studies looking at PD-1 therapies in combination.
Additionally, PARP inhibition for patients with tumors expressing DNA-repair defects is very promising. There is a trial out of the National Cancer Institute looking at the PARP inhibitor olaparib with the PD-1 inhibitor durvalumab. It is showing some promising results.
There is also currently a phase III study underway looking at enzalutamide plus atezolizumab, which is a PD-L1 inhibitor, and we should have results in under 5 years.
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