A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer

被引:47
作者
Ross, Ashley E. [1 ]
Hurley, Paula J. [1 ,2 ,3 ]
Tran, Phuoc T. [3 ,4 ,5 ]
Rowe, Steven P. [5 ]
Benzon, Benjamin [1 ]
Neal, Tanya O' [2 ,3 ]
Chapman, Carolyn [2 ,3 ]
Harb, Rana [2 ,3 ]
Milman, Yelena [2 ,3 ]
Trock, Bruce J. [1 ,2 ,3 ]
Drake, Charles G. [6 ]
Antonarakis, Emmanuel S. [1 ,2 ,3 ]
机构
[1] James Buchanan Brady Urol Inst, Johns Hopkins Sch Med, Dept Urol, Baltimore, MD 21205 USA
[2] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA
[3] Sidney Kimmel Canc Ctr, Johns Hopkins Sch Med, Baltimore, MD USA
[4] Johns Hopkins Sch Med, Dept Radiat Oncol, Baltimore, MD USA
[5] Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA
[6] Columbia Univ, Dept Med, New York, NY USA
关键词
ANDROGEN DEPRIVATION THERAPY; CELL INFILTRATION; DOUBLE-BLIND; IPILIMUMAB; IMMUNOTHERAPY; TESTOSTERONE; RADIOTHERAPY; RECOVERY; ANTIGEN; PLACEBO;
D O I
10.1038/s41391-019-0176-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 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.
引用
收藏
页码:184 / 193
页数:10
相关论文
共 37 条
[1]   Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers [J].
Abdo, Joe ;
Cornell, David L. ;
Mittal, Sumeet K. ;
Agrawal, Devendra K. .
FRONTIERS IN ONCOLOGY, 2018, 8
[2]   Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade [J].
Abida, Wassim ;
Cheng, Michael L. ;
Armenia, Joshua ;
Middha, Sumit ;
Autio, Karen A. ;
Vargas, Hebert Alberto ;
Rathkopf, Dana ;
Morris, Michael J. ;
Danila, Daniel C. ;
Slovin, Susan F. ;
Carbone, Emily ;
Barnett, Ethan S. ;
Hullings, Melanie ;
Hechtman, Jaclyn F. ;
Zehir, Ahmet ;
Shia, Jinru ;
Jonsson, Philip ;
Stadler, Zsofia K. ;
Srinivasan, Preethi ;
Laudone, Vincent P. ;
Reuter, Victor ;
Wolchok, Jedd D. ;
Socci, Nicholas D. ;
Taylor, Barry S. ;
Berger, Michael F. ;
Kantoff, Philip W. ;
Sawyers, Charles L. ;
Schultz, Nikolaus ;
Solit, David B. ;
Gopalan, Anuradha ;
Scher, Howard I. .
JAMA ONCOLOGY, 2019, 5 (04) :471-478
[3]  
Ahmed KA, 2012, FRONT ONCOL, V2, DOI [10.3389/fonc.2012.00215, 10.3389/fonc.2012.00172]
[4]   Cyclin-Dependent Kinase 12, Immunity, and Prostate Cancer [J].
Antonarakis, Emmanuel S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (11) :1087-1089
[5]   Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer [J].
Beer, Tomasz M. ;
Kwon, Eugene D. ;
Drake, Charles G. ;
Fizazi, Karim ;
Logothetis, Christopher ;
Gravis, Gwenaelle ;
Ganju, Vinod ;
Polikoff, Jonathan ;
Saad, Fred ;
Humanski, Piotr ;
Piulats, Josep M. ;
Gonzalez Mella, Pablo ;
Ng, Siobhan S. ;
Jaeger, Dirk ;
Parnis, Francis X. ;
Franke, Fabio A. ;
Puente, Javier ;
Carvajal, Roman ;
Sengelov, Lisa ;
McHenry, M. Brent ;
Varma, Arvind ;
van den Eertwegh, Alfonsus J. ;
Gerritsen, Winald .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (01) :40-+
[6]   Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer [J].
Benzon, Benjamin ;
Glavaris, Stephanie A. ;
Simons, Brian W. ;
Hughes, Robert M. ;
Ghabili, Kamyar ;
Mullane, Patrick ;
Miller, Rebecca ;
Nugent, Katriana ;
Shinder, Brian ;
Tosoian, Jeffrey ;
Fuchs, Ephraim J. ;
Tran, Phuoc T. ;
Hurley, Paula J. ;
Vuica-Ross, Milena ;
Schaeffer, Edward M. ;
Drake, Charles G. ;
Ross, Ashley E. .
PROSTATE CANCER AND PROSTATIC DISEASES, 2018, 21 (01) :126-136
[7]  
Boevé LMS, 2019, EUR UROL, V75, P410, DOI 10.1016/j.eururo.2018.09.008
[8]   Improved Survival with T Cell Clonotype Stability After Anti-CTLA-4 Treatment in Cancer Patients [J].
Cha, Edward ;
Klinger, Mark ;
Hou, Yafei ;
Cummings, Craig ;
Ribas, Antoni ;
Faham, Malek ;
Fong, Lawrence .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (238)
[9]   Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer [J].
Chi, Kim N. ;
Agarwal, Neeraj ;
Bjartell, Anders ;
Chung, Byung Ha ;
Pereira de Santana Gomes, Andrea J. ;
Given, Robert ;
Juarez Soto, Alvaro ;
Merseburger, Axel S. ;
Ozguroglu, Mustafa ;
Uemura, Hirotsugu ;
Ye, Dingwei ;
Deprince, Kris ;
Naini, Vahid ;
Li, Jinhui ;
Cheng, Shinta ;
Yu, Margaret K. ;
Zhang, Ke ;
Larsen, Julie S. ;
McCarthy, Sharon ;
Chowdhury, Simon .
NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (01) :13-24
[10]   Immunotherapy in Prostate Cancer: Teaching an Old Dog New Tricks [J].
Comiskey, Michael C. ;
Dallos, Matthew C. ;
Drake, Charles G. .
CURRENT ONCOLOGY REPORTS, 2018, 20 (09)