Background: Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer. Methods: This single-institution, pilot trial recruited 12 patients with newly diagnosed oligometastatic prostate cancer between 2015 and 2016. Patients underwent whole-prostate cryoablation combined with short-term androgen deprivation (eight months) and pembrolizumab (6 doses). The primary clinical endpoints were the number of patients with a PSA level of <0.6 ng/mL at one year and the frequency of adverse events. Other outcome measures included progression-free survival and systemic therapy-free survival. Exploratory analyses included PD-L1 protein expression. Results: Forty two percent (5/12) of patients had a PSAs of <0.6 ng/mL at one year though only 2 of these patients had recovered their testosterone at this time point. Median progression-free survival was 14 months, and median systemic therapy-free survival was 17.5 months. PD-L1 expression was not detectable by IHC in patients with evaluable tissue. All adverse events were grade ≤2, and there were no apparent complications from cryotherapy. Conclusions: Whole-prostate cryoablation combined with short-term androgen deprivation and pembrolizumab treatment was well tolerated and no safety concerns were observed in men with oligometastatic prostate cancer. Though local disease appeared effectively treated in the majority of men, the regimen only infrequency led to sustained disease control following testosterone recovery.
Bibliographical noteFunding Information:
Conflict of interest AER has previously been a consultant for Health-tronics. PTT has grant support from Astellas Pharm., RefleXion Medical, Inc and Bayer Healthcare; and has consulted for RefleXion Medical, Inc. CGD acknowledges stock or ownership interests in Compugen, Harpoon, Kleo, Potenza, and Tizona Therapeutics, and has served as a consultant for Agenus, Dendreon, Janssen Oncology, Eli Lilly, Merck, AstraZeneca, MedImmune, Pierre Fabre, Genentech, and Genocea Biosciences. ESA is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Medivation, AstraZeneca, Clovis, and Merck; he has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and he is the co-inventor of an AR-V7 biomarker technology that has been licensed to Qiagen. The other authors declare that they have no conflict of interest.
Acknowledgements We are grateful to the patients and their families for participating in this trial. This work was supported by PCF young investigator award (Ashley E. Ross) as well as partial funding from Merck and Healthtronics. Paula J. Hurley acknowledges support from the American Cancer Society (131356-RSG-17-160-01-CSM) and The National Cancer Institute/National Institute of Health RO1CA211695-01A1. P.T.T. acknowledges support from Ronald Rose, Joan Lazar, Movember Foundation, Prostate Cancer Foundation; NIH/NCI (R01CA166348, U01CA212007, U01CA231776 and R21CA223403). E.S.A. is partially funded by National Institutes of Health Cancer Center Support Grant P30 CA006973, and by Department of Defense grant W81XWH-16-PCRP-CCRSA.
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PubMed: MeSH publication types
- Clinical Trial
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.