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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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, χ ² 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, χ ² 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.

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil … (2017)

(177)Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients.

0 comments Cited 255 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study.

Dominik R. Berthold, Gregory R. Pond, Freidele Soban … (2008)

The TAX 327 study compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. Here, we report an updated analysis of survival. Investigators were asked to provide the date of death or last follow-up for all participants who were alive in August 2003. By March 2007, data on 310 additional deaths were obtained (total = 867 deaths). The survival benefit of D3P compared with MP has persisted with extended follow-up (P = .004). Median survival time was 19.2 months (95% CI, 17.5 to 21.3 months) in the D3P arm, 17.8 months (95% CI, 16.2 to 19.2 months) in the D1P arm, and 16.3 months (95% CI, 14.3 to 17.9 months) in the MP arm. More patients survived >/= 3 years in the D3P and D1P arms (18.6% and 16.6%, respectively) compared with the MP arm (13.5%). Similar trends in survival between treatment arms were seen for men greater than and less than 65 years of age, for those with and without pain at baseline, and for those with baseline PSA greater than and less than the median value of 115 ng/mL. The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients.

0 comments Cited 250 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer.

Scott Tagawa, Neeta Taskar, Shankar Vallabhajosula … (2013)

To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; (177)Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of (177)Lu-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers. Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received (177)Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. A single dose of (177)Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. ©2013 AACR.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Finn Edler von Eyben:

ORCID: http://orcid.org/0000-0001-8763-007X

45 66145862 , finn113edler@mail.tele.dk

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur. J. Nucl. Med. Mol. Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 16 December 2017

Publication date PMC-release: 16 December 2017

Publication date (Print): 2018

Volume: 45

Issue: 3

Pages: 496-508

Affiliations

[1 ]Center of Tobacco Control Research, Birkevej 17, DK 5230 Odense M, Denmark

[2 ]ISNI 0000 0004 1789 6237, GRID grid.416351.4, Department of Oncology, Medical Oncology Unit, , San Donato Hospital, ; Arezzo, Italy

[3 ]ISNI 0000 0001 1941 4308, GRID grid.5133.4, Department Medical, Surgery, and Health Sciences, , University of Trieste, ; Trieste, Italy

[4 ]Docrates Cancer Center, Helsinki, Finland

[5 ]GRID grid.410706.4, Department of Nuclear Medicine, , University Hospital Innsbruck, ; Innsbruck, Austria

Author information

Finn Edler von Eyben http://orcid.org/0000-0001-8763-007X

Article

Publisher ID: 3895

DOI: 10.1007/s00259-017-3895-x

PMC ID: 5787223

PubMed ID: 29247284

SO-VID: 58324a97-c19a-49e8-a058-133d5b72f8b4

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 2 August 2017

Date accepted : 20 November 2017

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: prostate cancer,177lu-psma radioligand therapy,abiraterone,enzalutamide,docetaxel,cabazitaxel,systematic review

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: prostate cancer, 177lu-psma radioligand therapy, abiraterone, enzalutamide, docetaxel, cabazitaxel, systematic review