Immunotherapy and the Future of Prostate Cancer Treatment
Despite early failures, there may be a role for single-agent and combination immunotherapy for patients with prostate cancer.
ORLANDO, FL – Despite early failures, there may be a role for single-agent and combination immunotherapy for patients with prostate cancer, according to a keynote presentation at 2017 Genitourinary Cancers Symposium.1
Charles G. Drake, MD, PhD, director of genitourinary oncology and co-director of immunotherapy at NewYork-Presbyterian/Columbia University Medical Center in New York, New York, reviewed the potential role of PD-1/PD-L1 inhibition, CTLA-4 blockade, combined PD-1 and CTLA-4 blockade, and vaccines as treatments for prostate cancer.
Prostate cancer has a low mutation rate and limited infiltrating CD8 T cells compared with melanoma and non-small cell lung cancer, where PD-1/PD-L1 blockade is effective. A phase 1b trial of nivolumab in 17 patients with advanced prostate cancer, for example, showed no objective responses with anti-PD-1 antibody therapy.
Dr Drake described encouraging preliminary findings from a phase 2 study (Clinical Trials.gov Identifier: NCT02312557) presented at the European Society for Medical Oncology (ESMO) Congress 2017, which showed clinical activity with PD-1 blockade with pembrolizumab plus enzalutamide in some patients with enzalutamide-refractory, metastatic, castrate-resistance prostate cancer (mCRPC).
"These were real responses and I think this was really revelatory because it showed that in men with enzalutamide-refractory, castration-resistant disease, there could be objective and PSA responses to monotherapy PD-1 blockade at least when added to enzalutamide," said Dr Clark. "To me, this was one of the highlights of the year."
Combined PD-1 and CTLA-4 blockade may also be promising and is being evaluated by Dr Clark and his colleagues in the STARVE-PC trial (ClinicalTrials.gov Identifier: NCT02601014), a biomarker-driven phase 2 study of ipilimumab plus nivolumab followed by nivolumab maintenance in AR-V7-expressing mCRPC.
"It is important to remember that this regimen is reasonably toxic. The rate of grade 3 to 4 adverse events ranges from 40% to 60%, which could be why we had trouble getting enthusiasm to open such a trial," Dr Clark added. "We should probably have some data on this study in a year or so. We are following these patients closely."
Dr Clark discussed additional investigational immunotherapeutic strategies for prostate cancer, including vaccines based on attenuated Listeria monocytogenes, bone-directed radiation, and cryotherapy.
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A pilot study (ClinicalTrials.gov Identifier: NCT02489357) for patients with hormone-naïve oligo-metastatic prostate cancer is assessing degarelix monthly for 8 months with cryoablation of the prostate at 1 month and pembrolizumab every 3 weeks for months 1 to 5. That study completed enrollment with 12 patients.
- Drake CG. Immunotherapy for Prostate Cancer. Lecture presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.