Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Urology Reports
Erschienen in: Current Urology Reports 10/2019

01.10.2019 | Prostate Cancer (S Prasad, Section Editor)

Immunotherapy in Metastatic Castration-Resistant Prostate Cancer: Past and Future Strategies for Optimization

verfasst von: Melissa A. Reimers, Kathryn E. Slane, Russell K. Pachynski

Erschienen in: Current Urology Reports | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

To date, prostate cancer has been poorly responsive to immunotherapy. In the current review, we summarize and discuss the current literature on the use of vaccine therapy and checkpoint inhibitor immunotherapy in metastatic castration-resistant prostate cancer (mCRPC).

Recent Findings

Sipuleucel-T currently remains the only FDA-approved immunotherapeutic agent for prostate cancer. Single-agent phase 3 vaccine trials with GVAX and PROSTVAC have failed to demonstrate survival benefit to date. Clinical trials using combination approaches, including combination PROSTVAC along with a neoantigen vaccine and checkpoint inhibitor immunotherapy, are ongoing. Checkpoint inhibitor monotherapy clinical trials have demonstrated limited efficacy in advanced prostate cancer, and combination approaches and molecular patient selection are currently under investigation.

Summary

The optimal use of vaccine therapy and checkpoint inhibitor immunotherapy in metastatic castration-resistant prostate cancer remains to be determined. Ongoing clinical trials will continue to inform future clinical practice.
Literatur
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRef
2.
Kelly SP, Anderson WF, Rosenberg PS, Cook MB. Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus. 2018;4(1):121–7.CrossRefPubMed
3.
Hurwitz AA, Foster BA, Kwon ED, Truong T, Choi EM, Greenberg NM, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res. 2000;60(9):2444–8.PubMed
4.
van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti- cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999;190(3):355–66.CrossRefPubMedPubMedCentral
5.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.CrossRefPubMedPubMedCentral
6.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.CrossRefPubMed
7.
Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–92.CrossRefPubMed
8.
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040–51.CrossRef
9.
Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow- up in KEYNOTE-012. Br J Cancer. 2018;119(2):153–9.CrossRefPubMedPubMedCentral
10.
Balar AV, Castellano D, O'Donnell PH, Grivas P, Vuky J, Powles T, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(11):1483–92.CrossRef
11.
• Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. 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 Clin Oncol. 2017;35(1):40–7 Randomized, placebo-controlled phase III clinical trial of 598 patients with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC. Patients were randomized 2:1 to receive ipilimumab 10 mg/kg IV every 3 weeks or placebo. Primary endpoint of overall survival was not met. CrossRefPubMed
12.
• Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(7):700–12 Randomized, placebo-controlled phase III clinical trial of 799 mCRPC patients with progression on docetaxel chemotherapy. Patients received 8 Gy radiation directed to an osseous metastasis followed by either ipilimumab 10 mg/kg IV every 3 weeks or placebo. Primary endpoint of overall survival was not met. CrossRefPubMedPubMedCentral
13.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8.CrossRefPubMedPubMedCentral
14.
Danaher P, Warren S, Lu R, Samayoa J, Sullivan A, Pekker I, et al. Pan-cancer adaptive immune resistance as defined by the tumor inflammation signature (TIS): results from The Cancer Genome Atlas (TCGA). J Immunother Cancer. 2018;6(1):63.CrossRefPubMedPubMedCentral
15.
Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, et al. Placebo- controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006;24(19):3089–94.CrossRefPubMed
16.
Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115(16):3670–9.CrossRefPubMed
17.
•• Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22 Randomized, placebo-controlled phase III clinical trial of 512 patients with asymptomatic or minimally symptomatic mCRPC. Patients were randomized 2:1 to receive sipuleucel-T or placebo. The study met its primary endpoint of overall survival, with a median survival of 25.8 months in the sipuleucel-T arm and 21.7 months in the control arm, for a benefit of 4.1 months. Sipuleucel-T was FDA approved in 2010. CrossRef
18.
Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the immunotherapy for prostate adenocarcinoma treatment (IMPACT) trial. Urology. 2013;81(6):1297–302.CrossRefPubMed
19.
Holl EK, McNamara MA, Healy P, Anand M, Concepcion RS, Breland CD, et al. Prolonged PSA stabilization and overall survival following sipuleucel-T monotherapy in metastatic castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis. 2019.
20.
Sartor AO, Armstrong A, Ahaghotu C, McLeod D, Cooperberg M, Penson D, et al. PD24-12 overall survival analysis of African American and Caucasian patients receiving sipuleucel-T: preliminary data from the proceed registry. J Urol. 2017;197(4S):e456–e7.CrossRef
21.
Twardowski P, Wong JYC, Pal SK, Maughan BL, Frankel PH, Franklin K, et al. Randomized phase II trial of sipuleucel-T immunotherapy preceded by sensitizing radiation therapy and sipuleucel-T alone in patients with metastatic castrate resistant prostate cancer. Cancer Treat Res Commun. 2019;19:100116.CrossRefPubMed
22.
Fong L, Carroll P, Weinberg V, Chan S, Lewis J, Corman J, et al. Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer. J Natl Cancer Inst. 2014;106(11).
23.
Caram MEV, Ross R, Lin P, Mukherjee B. Factors associated with use of sipuleucel-T to treat patients with advanced prostate cancer. JAMA Netw Open. 2019;2(4):e192589.CrossRefPubMedPubMedCentral
24.
Simons JW, Carducci MA, Mikhak B, Lim M, Biedrzycki B, Borellini F, et al. Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naive prostate cancer. Clin Cancer Res. 2006;12(11 Pt 1):3394–401.CrossRefPubMed
25.
Madan RA, Arlen PM, Mohebtash M, Hodge JW, Gulley JL. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs. 2009;18(7):1001–11.CrossRefPubMedPubMedCentral
26.
Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099–105.CrossRefPubMedPubMedCentral
27.
Kantoff PWGJ, Pico-Navarro C. Revised overall survival analysis of a phase II, randomized, double- blind, controlled study of PROSTVAC in men with metastatic castration-resistant prostate cancer. J Clin Oncol. 2017;35:124–5.CrossRefPubMed
28.
• Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, et al. Phase III Trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(13):1051–61 Randomized, placebo-controlled phase III clinical trial of 864 patients with mCRPC randomized to receive PROSTVAC + GM-CSF or placebo. The primary endpoint was overall survival, and the study was halted prematurely at the third interim analysis due to futility. CrossRefPubMed
29.
Hansen AR, Massard C, Ott PA, Haas NB, Lopez JS, Ejadi S, et al. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. Ann Oncol. 2018;29(8):1807–13.CrossRefPubMed
30.
Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol. 2011;11(5):330–42.CrossRef
31.
Johnson LE, Brockstedt D, Leong M, Lauer P, Theisen E, Sauer JD, et al. Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA and Listeria vaccines elicits superior anti-tumor immunity dependent on CD4+ T cells elicited by DNA priming. Oncoimmunology. 2018;7(8):e1456603.CrossRefPubMedPubMedCentral
32.
Hannan R, Zhang H, Wallecha A, Singh R, Liu L, Cohen P, et al. Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer. Cancer Immunol Immunother. 2012;61(12):2227–38.CrossRefPubMed
33.
NBea H. Phase I-II study of ADXS31-142 alone and in combination with pembrolizumab in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC): the KEYNOTE- 046 trial. J Immunother Cancer. 2015;3(Suppl2):P153.
34.
Mkrtichyan M, Chong N, Abu Eid R, Wallecha A, Singh R, Rothman J, et al. Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy. J Immunother Cancer. 2013;1:15.CrossRefPubMedPubMedCentral
35.
Rekoske BT, Smith HA, Olson BM, Maricque BB, McNeel DG. PD-1 or PD-L1 blockade restores antitumor efficacy following SSX2 epitope-modified DNA vaccine immunization. Cancer Immunol Res. 2015;3(8):946–55.CrossRefPubMedPubMedCentral
36.
Zahm CD, Colluru VT, McNeel DG. Vaccination with high-affinity epitopes impairs antitumor efficacy by increasing PD-1 expression on CD8(+) T cells. Cancer immunology research. 2017;5(8):630–41.CrossRefPubMedPubMedCentral
37.
McNeel DG, Eickhoff JC, Wargowski E, Zahm C, Staab MJ, Straus J, et al. Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2018;9(39):25586–96.CrossRefPubMedPubMedCentral
38.
Lambricht L, Lopes A, Kos S, Sersa G, Preat V, Vandermeulen G. Clinical potential of electroporation for gene therapy and DNA vaccine delivery. Expert Opin Drug Deliv. 2016;13(2):295–310.CrossRefPubMed
39.
de Bono JS. KEYNOTE-199: Pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology. 2018;36(15):suppl.5007.CrossRef
40.
Padmanee S, Russel KP, Vivek N, Aude F, Gwenaelle G, Matt DG, et al. Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC; CheckMate 650). Journal of Clinical Oncology. 2019;37(7):suppl.142.
41.
Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, et al. Early evidence of anti- PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016;7(33):52810–7.CrossRefPubMedPubMedCentral
42.
Bishop JL, Sio A, Angeles A, Roberts ME, Azad AA, Chi KN, et al. PD-L1 is highly expressed in enzalutamide resistant prostate cancer. Oncotarget. 2015;6(1):234–42.CrossRefPubMed
43.
Fong P. Keynote-365 cohort C: Pembrolizumab (pembro) plus enzalutamide (enza) in abiraterone (abi)-pretreated patients (pts) with metastatic castrate resistant prostate cance (mCRPC). Journal of Clinical Oncology. 2019;37(7):suppl (March 1 2019)):171.CrossRef
44.
Gevensleben H, Dietrich D, Golletz C, Steiner S, Jung M, Thiesler T, et al. The immune checkpoint regulator PD-L1 is highly expressed in aggressive primary prostate cancer. Clin Cancer Res. 2016;22(8):1969–77.CrossRefPubMed
45.
•• Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;162(2):454 Comprehensive analysis of the genomic landscape of 150 patients with mCRPC. Aberrations of AR , ETS genes, TP53 and PTEN were most frequent. CrossRef
46.
Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. 2018;175(3):889.CrossRefPubMed
47.
Antonarakis ES, Shaukat F, Isaacsson Velho P, Kaur H, Shenderov E, Pardoll DM, et al. Clinical features and therapeutic outcomes in men with advanced prostate cancer and DNA mismatch repair gene mutations. Eur Urol. 2019;75(3):378–82.CrossRefPubMed
48.
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13.CrossRefPubMedPubMedCentral
49.
Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019;5(4):471-8.
50.
Karzai F, VanderWeele D, Madan RA, Owens H, Cordes LM, Hankin A, et al. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 2018;6(1):141.CrossRefPubMedPubMedCentral
51.
Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, et al. Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Oncotarget. 2018;9(47):28561–71.CrossRefPubMedPubMedCentral
52.
• Wu YM, Cieslik M, Lonigro RJ, Vats P, Reimers MA, Cao X, et al. Inactivation of CDK12 delineates a distinct immunogenic class of advanced prostate cancer. Cell. 2018;173(7):1770–82 e14 CDK12 loss has been identified as a novel subtype of mCRPC, characterized by focal tandem duplications and increased gene fusions. CrossRefPubMed
53.
Massari F, Ciccarese C, Calio A, Munari E, Cima L, Porcaro AB, et al. Magnitude of PD-1, PD-L1 and T lymphocyte expression on tissue from castration-resistant prostate adenocarcinoma: an exploratory analysis. Target Oncol. 2016;11(3):345–51.CrossRefPubMed
54.
Metadaten
Titel
Immunotherapy in Metastatic Castration-Resistant Prostate Cancer: Past and Future Strategies for Optimization
verfasst von
Melissa A. Reimers
Kathryn E. Slane
Russell K. Pachynski
Publikationsdatum
01.10.2019
Verlag
Springer US
Erschienen in
Current Urology Reports / Ausgabe 10/2019
Print ISSN: 1527-2737
Elektronische ISSN: 1534-6285
DOI
https://doi.org/10.1007/s11934-019-0931-3

Weitere Artikel der Ausgabe 10/2019

Current Urology Reports 10/2019 Zur Ausgabe

New Imaging Techniques (S Rais-Bahrami and K Porter, Section Editors)

Irreversible Electroporation for the Ablation of Prostate Cancer

New Imaging Techniques (S Rais-Bahrami and K Porter, Section Editors)

Developing a National Center of Excellence for Prostate Imaging

Lower Urinary Tract Symptoms & Voiding Dysfunction (J Sandhu, Section Editor)

The Complex Relationship Between Lower Urinary Tract Symptoms and Sexual Health

Prostate Cancer (S Prasad, Section Editor)

The Use of Multiparametric Magnetic Resonance Imaging (mpMRI) in the Detection, Evaluation, and Surveillance of Clinically Significant Prostate Cancer (csPCa)

Education (G Badalato, Section Editor)

What Is Underlying Resident Burnout in Urology and What Can Be Done to Address this?

Prostate Cancer (S Prasad, Section Editor)

Quality of Life–Focused Decision-Making for Prostate Cancer

Neu im Fachgebiet Urologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise