San Antonio, Texas USA (UroToday.com) Immunotherapy treatment for prostate cancer has been quite limited given that currently Sipuleucel-T is the only immunotherapy approved for the management of castrate resistant prostate cancer. With the introduction of check-point inhibitors there has been a growing interest in the use of this type of therapies in patients with advanced prostate cancer.
In this session Dr. Yu from the Seattle Cancer Care Alliance presented the current landscape of immunotherapy in the treatment of advanced prostate cancer. The use of immunotherapy for the management of advance prostate cancer has been quite limited due to the limited use of Sipuleucel-T in the clinical setting. Sipuleucel-T is only approved in select cohort of patients with mildly symptomatic castrate resistant prostate cancer, which provides a very short window of opportunity. The effect of the treatment is challenging to follow due to the poor PSA response to therapy, with no response on progression-free survival (PFS) and 4 month improvement on overall survival (OS). In a post-hoc analysis of the Sipuleucel-T trial showed that for the immune system to be able to combat the cancer it requires a small tumor burden, showing the highest survival in patients with PSA levels < 25 pg/mL.
Small trials on check-point inhibitors have not shown the improvement in OS seen in other GU malignancies such as kidney or bladder, which have blunted the excitement on the use of checkpoint inhibitors in prostate cancer. Reasoning behind the lack of effect of check-point inhibitors was the low expression of PD-L1 in prostate cancer along with the low tumor mutation rates. In further review of the available data there appears to be an increase expression of PD-L1 in high risk tumors, which appear to be diluted down in prior studies. A recent abstract presented at ESMO, showed improved responses, some durable, in patients treated with Pembrolizumab who on selection was found to have significant expression of the PD-L1 ligand. A recent study from the University of British Columbia, looked at the expression of PD-L1/2 in the dendritic cells of patients treated with Enzalutamide. Interestingly, the dendritic expression of PD-L1/2 appeared to increase in those patients treated with Enzalutamide who were progressing on therapy. In follow-up study Pembrolizumab was added to patients failing Enzalutamide therapy showing a significant reduction in PSA levels.
Given the limited cohort of patients in which immunotherapy appears to be effective there are several ongoing trials looking into immune system priming with the use of chemotherapy and radiation to release neo-antigens for dendritic cell priming. There are also some early work on combination therapy with Pembrolizumab + docetaxel/Enzalutamide which may improve response.
In summary, there is some encouraging early studies that show that immunotherapy have a niche in a select group of patients with advance prostate cancer that could be expanded with immune system priming and combination therapy.
Presented By: Evan Y. Yu, MD, Seattle Cancer Care Alliance
Written By: Andres F. Correa, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA