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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2018

Open Access 01-03-2018 | Review Article

Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

Authors: Finn Edler von Eyben, Giandomenico Roviello, Timo Kiljunen, Christian Uprimny, Irene Virgolini, Kalevi Kairemo, Timo Joensuu

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2018

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Abstract

Aims

There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743).

Methods

The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.​gov indicated ongoing studies. The meta-analysis used the random-effects model.

Results

Twelve studies including 669 patients reported 177Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177Lu-PSMA RLT. The treatment with 177Lu-PSMA-617 and 177Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ2 test). Median survival was longer after 177Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ2 test).

Conclusions

As for patients with mCRPC, treatment with 177Lu-PSMA-617 RTL and 177Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.
Literature
1.
Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61:1079–92.CrossRefPubMed
2.
Patrikidou A, Loriot Y, Eymard JC, Albiges L, Massard C, Ileana E, et al. Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17:348–52.CrossRefPubMed
3.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.CrossRefPubMed
4.
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.CrossRefPubMed
5.
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.CrossRefPubMedPubMedCentral
6.
Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.CrossRefPubMed
7.
Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15:738–46.CrossRefPubMed
8.
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;363:411–22.CrossRefPubMed
9.
Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26:242–5.CrossRefPubMed
10.
Summers N, Vanderpuye-Orgle J, Reinhart M, Gallagher M, Sartor O. Efficacy and safety of post-docetaxel therapies in metastatic castration-resistant prostate cancer: a systematic review of the literature. Curr Med Res Opin. 2017:1–14.
11.
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42.CrossRefPubMed
12.
Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R, et al. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol 2017.
13.
Kopka K, Benesova M, Barinka C, Haberkorn U, Babich J. Glu-Ureido-based inhibitors of prostate-specific membrane antigen: lessons learned during the development of a novel class of low-molecular-weight Theranostic radiotracers. J Nucl Med. 2017;58:17S–26S.CrossRefPubMed
14.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37.CrossRefPubMed
15.
von Eyben FE, Picchio M, von Eyben R, Rhee H, Bauman G. 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography for prostate cancer: a systematic review and meta-analysis. Eur Urol Focus 2016.
16.
Calopedos RJS, Chalasani V, Asher R, Emmett L, Woo HH. Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and ligands for the treatment of metastatic castrate-resistant prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017;20:352–60.CrossRefPubMed
17.
Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA Radioligand therapy for prostate cancer. J Nucl Med. 2017;58:1196–200.CrossRefPubMed
18.
von Eyben FE, Kiljunen T, Joensuu T, Kairemo K, Uprimny C, Virgolini I. 177Lu-PSMA-617 radioligand therapy for a patient with lymph node metastatic prostate cancer. Oncotarget. 2017;8:66112–6.
19.
Gillessen S, de Bono JS, Sartor O, Omlin AG. Reply to Finn E. von Eyben, Irene Virgolini and Giandomenico Roviello’s Letter to the Editor re: Silke Gillessen, Gerhardt Attard, Tomasz M. Beer, et al. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol. In press. https://​doi.​org/​10.​1016/​j.​eururo.​2017.​06.​002. Eur Urol. 2017.
20.
21.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151:W65–94.CrossRefPubMed
22.
Maines F, Caffo O, Veccia A, Trentin C, Tortora G, Galligioni E, et al. Sequencing new agents after docetaxel in patients with metastatic castration-resistant prostate cancer. Crit Rev Oncol Hematol. 2015;96:498–506.CrossRefPubMed
23.
Roviello G, Petrioli R, Laera L, Francini E. The third line of treatment for metastatic prostate cancer patients: option or strategy? Crit Rev Oncol Hematol. 2015;95:265–71.CrossRefPubMed
24.
Caffo O, De Giorgi U, Fratino L, Alesini D, Zagonel V, Facchini G, et al. Clinical outcomes of castration-resistant prostate cancer treatments administered as third or fourth line following failure of docetaxel and other second-line treatment: results of an Italian multicentre study. Eur Urol. 2015;68:147–53.CrossRefPubMed
25.
Brasso K, Thomsen FB, Schrader AJ, Schmid SC, Lorente D, Retz M, et al. Enzalutamide antitumour activity against metastatic castration-resistant prostate cancer previously treated with docetaxel and Abiraterone: a multicentre analysis. Eur Urol. 2015;68:317–24.CrossRefPubMed
26.
Scher HI, Morris MJ, Basch E, Heller G. End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice. J Clin Oncol. 2011;29:3695–704.CrossRefPubMedPubMedCentral
27.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
28.
Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.CrossRefPubMed
29.
30.
Bander NH, Milowsky MI, Nanus DM, Kostakoglu L, Vallabhajosula S, Goldsmith SJ. Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol. 2005;23:4591–601.CrossRefPubMed
31.
Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, et al. Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013;19:5182–91.CrossRefPubMedPubMedCentral
32.
Heck MM, Retz M, D’Alessandria C, Rauscher I, Scheidhauer K, Maurer T, et al. Systemic Radioligand therapy with (177)Lu labeled prostate specific membrane antigen ligand for imaging and therapy in patients with metastatic castration resistant prostate cancer. J Urol. 2016;196:382–91.CrossRefPubMed
33.
Kratochwil C, Giesel FL, Stefanova M, Benesova M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.CrossRefPubMed
34.
Kulkarni HR, Singh A, Schuchardt C, Niepsch K, Sayeg M, Leshch Y, et al. PSMA-based Radioligand therapy for metastatic castration-resistant prostate cancer: the Bad Berka experience since 2013. J Nucl Med. 2016;57:97S–104S.CrossRefPubMed
35.
Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kurpig S, Eppard E, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44:1448–54.CrossRefPubMed
36.
Brauer A, Grubert LS, Roll W, Schrader AJ, Schafers M, Bogemann M, et al. 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1663–70.CrossRefPubMed
37.
Fendler WP, Reinhardt S, Ilhan H, Delker A, Boning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8:3581–90.CrossRefPubMed
38.
Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 Radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2017;58:85–90.CrossRefPubMed
39.
Rahbar K, Boegemann M, Yordanova A, Eveslage M, Schafers M, Essler M, et al. PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival. Eur J Nucl Med Mol Imaging. 2018;45:12–9.
40.
Scarpa L, Buxbaum S, Kendler D, Fink K, Bektic J, Gruber L, et al. The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates. Eur J Nucl Med Mol Imaging. 2017;44:788–800.CrossRefPubMed
41.
Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A, et al. 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44:81–91.CrossRefPubMed
42.
Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pezaro C, et al. Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol. 2013;24:1807–12.CrossRefPubMed
43.
Noonan KL, North S, Bitting RL, Armstrong AJ, Ellard SL, Chi KN. Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide. Ann Oncol. 2013;24:1802–7.CrossRefPubMed
44.
Pezaro CJ, Omlin AG, Altavilla A, Lorente D, Ferraldeschi R, Bianchini D, et al. Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. Eur Urol. 2014;66:459–65.CrossRefPubMed
45.
Sella A, Sella T, Peer A, Berger R, Frank SJ, Gez E, et al. Activity of cabazitaxel after docetaxel and abiraterone acetate therapy in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2014;12:428–32.CrossRefPubMed
46.
Al Nakouzi N, Le Moulec S, Albiges L, Wang C, Beuzeboc P, Gross-Goupil M, et al. Cabazitaxel remains active in patients progressing after docetaxel followed by novel androgen receptor pathway targeted therapies. Eur Urol. 2015;68:228–35.CrossRefPubMed
47.
Azad AA, Eigl BJ, Murray RN, Kollmannsberger C, Chi KN. Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol. 2015;67:23–9.CrossRefPubMed
48.
Cheng HH, Gulati R, Azad A, Nadal R, Twardowski P, Vaishampayan UN, et al. Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel. Prostate Cancer Prostatic Dis. 2015;18:122–7.CrossRefPubMedPubMedCentral
49.
Sonpavde G, Bhor M, Hennessy D, Bhowmik D, Shen L, Nicacio L, et al. Sequencing of Cabazitaxel and Abiraterone acetate after docetaxel in metastatic castration-resistant prostate cancer: treatment patterns and clinical outcomes in multicenter community-based US oncology practices. Clin Genitourin Cancer. 2015;13:309–18.CrossRefPubMed
50.
Wissing MD, Coenen JL, van den Berg P, Westgeest HM, van den Eertwegh AJ, van Oort IM, et al. CAST: a retrospective analysis of cabazitaxel and abiraterone acetate sequential treatment in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel. Int J Cancer. 2015;136:E760–72.CrossRefPubMed
51.
Badrising SK, van der Noort V, van den Eertwegh AJ, Hamberg P, van Oort IM, van den Berg HP, et al. Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation. Prostate. 2016;76:32–40.CrossRefPubMed
52.
Davies RS, Smith C, Lester JF. Third-line enzalutamide following docetaxel and Abiraterone in metastatic castrate-resistant prostate cancer. Anticancer Res. 2016;36:1799–803.PubMed
53.
Kongsted P, Svane IM, Lindberg H, Bisbjerg R, Daugaard G, Sengelov L. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer. Anti-Cancer Drugs. 2016;27:695–701.CrossRefPubMed
54.
Bando Y, Hinata N, Terakawa T, Furukawa J, Harada KI, Nakano Y, et al. Activity of cabazitaxel in patients with metastatic castration-resistant prostate cancer after treatment with single or dual regimens of novel androgen receptor-targeting agents. Med Oncol. 2017;34:163.CrossRefPubMed
55.
de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, et al. Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with Abiraterone acetate plus prednisone for >/=24 weeks in Europe. Eur Urol 2017.
56.
Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J. Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64:52–60.CrossRefPubMedPubMedCentral
57.
Fendler WP, Kratochwil C, Ahmadzadehfar H, Rahbar K, Baum RP, Schmidt M, et al. 177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer. Nuklearmedizin. 2016;55:123–8.PubMed
58.
Rathke H, Giesel FL, Flechsig P, Kopka K, Mier W, Hohenfellner M, et al. Repeated Lu-177-PSMA-617 radioligand therapy using treatment activities up to 9.3 GBq. J Nucl Med. 2017.
59.
Eisenberger M, Hardy-Bessard AC, Kim CS, Geczi L, Ford D, Mourey L, et al. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. J Clin Oncol. 2017;135:3198–206.
60.
Wei X, Schlenkhoff C, Schwarz B, Essler M, Ahmadzadehfar H. Combination of 177Lu-PSMA-617 and external radiotherapy for the treatment of cerebral metastases in patients with castration-resistant metastatic prostate cancer. Clin Nucl Med. 2017;42:704–6.CrossRefPubMed
61.
62.
Estevez SV, Herranz UA, Calvo OF, Afonso Afonso FJ, Couto LS, Quintela ML, et al. Prostate cancer perspectives after chaarted: optimizing treatment sequence. Crit Rev Oncol Hematol. 2016;107:119–27.CrossRefPubMed
63.
Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.CrossRefPubMed
64.
Taplin ME, Armstrong AJ, Lin P, Krivoshik A, Phung, Parli T, et al. Clinical Outcomes of Chemotherapy-Naive Men with Metastatic Castration-Resistant Prostate Cancer and Low Baseline PSA Treated with Enzalutamide vs Placebo. J Urol. 2017;198:1324–32.
65.
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.CrossRefPubMed
66.
Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.CrossRefPubMedPubMedCentral
67.
Poorthuis MHF, Vernooij RWM, van Moorselaar RJA, de Reijke TM. First-line non-cytotoxic therapy in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of 10 randomised clinical trials. BJU Int. 2017;119:831–45.CrossRefPubMed
Metadata
Title
Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review
Authors
Finn Edler von Eyben
Giandomenico Roviello
Timo Kiljunen
Christian Uprimny
Irene Virgolini
Kalevi Kairemo
Timo Joensuu
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3895-x

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