Efficacy and side effects of lutetium-¹⁷⁷PSMA-617 in patients with castration resistant metastatic prostate cancer: a systematic review and meta-analysis

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Рұқсат ақылы немесе тек жазылушылар үшін

Аннотация

Introduction. Progression of metastatic prostate cancer after castration resistance is one of the main challenges in prostate cancer therapy. ¹⁷⁷Lu-PSMA-617 has been recently investigated in castration resistant metastatic prostate cancer.

Objectives. To systematically evaluate the efficacy and safety profile of ¹⁷⁷Lu-PSMA- 617.

Patients and methods. A systematic review and meta-analysis was conducted according PRISMA principles. From initial 261 results, 3 randomized controlled trials met our inclusion criteria. The primary outcome of this study was oncological response and side effects. RevMan 5,4 software was applied in this systematic review and meta- analysis.

Results. A total of 1071 patients were included in the pooled analysis. 670 (62,6%) patients received ¹⁷⁷Lu-PSMA-617. Progression-free survival was significantly better with a hazard ratio of 0,72 (p= 0,00001). 50%>PSA reduction reported in 75 (63%) vs. 45/121 patients (37,2%) (p=0,0001). Total adverse events recorded in 572 / 627 (91,2%) developed AEs, vs. 204 / 290 (70,3%) (p = 0,00001). Fatigue was reported in 306/647 (47,3%) patients vs 88/310 (28,4%) (p=0,00001). And constipation in 110/549 (20%) vs 24/225 (10,7%) (p=0,003). Both thrombocytopenia and leucopoenia were marginally significantly higher in 114 / 647 (17,6%) vs 19 / 310 (6,1%) (p=0,08) and 81 / 647 (12,5%) vs 13 / 310 (4,2%) (p=0,10), respectively.

Conclusion. ¹⁷⁷Lu-PSMA-617 results in significant reduction in PSA and improves the progression-free survival. It can cause tolerable side effects, mainly fatigue, constipation, thrombocytopenia and leucopoenia.

Толық мәтін

Рұқсат жабық

Авторлар туралы

Omar Fahmy

Department of Urology, Faculty of Medicine and Science Health Universiti Putra; Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Хат алмасуға жауапты Автор.
Email: omarfahmy.ahmed@upm.edu.my
ORCID iD: 0000-0002-1631-2733

MBBS, MRCS (England), Masters Urology (Zagazig), FRCS Urology (Glasgow), Associate Professor and Consultant Urologist of Department of Urology, Faculty of Medical Science and Health

 

Малайзия, Malaysia; Persiaran Mardi-UPM, 43400 Serdang, Malaysia

Razaleigh Mohd

Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Email: razaleighyusof@yahoo.com
ORCID iD: 0000-0003-1596-9415

M.D., MMed Surgery, FRCS Urology, Consultant Urologist Department of Urology, Hospital Sultan Abdul Aziz Shah

Малайзия, Persiaran Mardi-UPM, 43400 Serdang, Malaysia

Mohd Khairul Asri

Department of Urology, Faculty of Medicine and Science Health Universiti Putra; Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Email: drkhairulasri@gmail.com
ORCID iD: 0000-0002-5026-5432

M.D., Masters Surgery, FRCS Urology, Professor and Consultant Urologist Department of Urology, Faculty Medicine and Science Health

Малайзия, Malaysia; Persiaran Mardi-UPM, 43400 Serdang, Malaysia

Әдебиет тізімі

  1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/CAAC.21492
  2. Cornford P., van den Bergh R.C.N., Briers E., Van den Broeck T., Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S., Grivas N., Grummet J., Henry A.M., der Kwast T.H.V., Lam T.B., Lardas M., Liew M., Mason M.D., Moris L., Oprea-Lager D.E., der Poel H.G.V., Rouvière O., Schoots I.G., Tilki D., Wiegel T., Willemse P.M., Mottet N. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2021 Feb;79(2):263-282. doi: 10.1016/j.eururo.2020.09.046. Epub 2020 Oct 7. PMID: 33039206.
  3. Heidenreich A., Bastian P.J., Bellmunt J., Bolla M., Joniau S., van der Kwast T., Mason M., Matveev V., Wiegel T., Zattoni F., Mottet N.; European Association of Urology. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014 Feb;65(2):467-79. doi: 10.1016/j.eururo.2013.11.002. Epub 2013 Nov 12. PMID: 24321502.
  4. James N.D., Sydes M.R., Clarke N.W., Mason M.D., Dearnaley D.P., Spears M.R., Ritchie A.W., Parker C.C., Russell J.M., Attard G., de Bono J., Cross W., Jones R.J., Thalmann G., Amos C., Matheson D., Millman R., Alzouebi M., Beesley S., Birtle A.J., Brock S., Cathomas R., Chakraborti P., Chowdhury S., Cook A., Elliott T., Gale J., Gibbs S., Graham J.D., Hetherington J., Hughes R., Laing R., McKinna F., McLaren D.B., O’Sullivan J.M., Parikh O., Peedell C., Protheroe A., Robinson A.J., Srihari N., Srinivasan R., Staffurth J., Sundar S., Tolan S., Tsang D., Wagstaff J., Parmar M.K.; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. doi: 10.1016/S0140-6736(15)01037-5. Epub 2015 Dec 21. PMID: 26719232; PMCID: PMC4800035.
  5. Sweeney C.J., Gillessen S., Rathkopf D. et al. Abstract CT014: IMbassador250: A phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). Cancer Res. 2020;80(16 Supplement):CT014-CT014. doi: 10.1158/1538-7445.AM2020-CT014
  6. Chung D.Y., Ha J.S., Cho K.S. Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer. Biomedicines. 2021 Jun 9;9(6):661. doi: 10.3390/biomedicines9060661. PMID: 34207755; PMCID: PMC8229358.
  7. Gudkov S.V., Shilyagina N.Y., Vodeneev V.A., Zvyagin A. v. Targeted Radionuclide Therapy of Human Tumors. International Journal of Molecular Sciences. 2016;17:33. doi: 10.3390/IJMS17010033
  8. Jones W., Griffiths K., Barata P.C., Paller C.J. PSMA Theranostics: Review of the Current Status of PSMA-Targeted Imaging and Radioligand Therapy. Cancers. 2020;12(6):1367. doi: 10.3390/CANCERS12061367
  9. Jeitner T.M., Babich J.W., Kelly J.M. Advances in PSMA theranostics. Transl Oncol. 2022;22:101450. doi: 10.1016/J.TRANON.2022.101450
  10. Sadaghiani M.S., Sheikhbahaei S., Werner R.A. et al. A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177–labeled Prostate-specific Membrane Antigen–targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. Eur Urol. 2021;80(1):82-94. doi: 10.1016/J.EURURO.2021.03.004
  11. Sartor O., de Bono J., Chi K.N. et al. Lutetium-177–PSMA-617 for Metastatic Castration- Resistant Prostate Cancer. New England Journal of Medicine. 2021;385(12):1091-1103. doi: 10.1056/NEJMOA2107322/SUPPL_FILE/NEJMOA2107322_DATA-SHARING.PDF
  12. Moher D., Shamseer L., Clarke M., Ghersi D., Liberati A., Petticrew M., Shekelle P., Stewart L.A.; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan 1;4(1):1. doi: 10.1186/2046-4053-4-1. PMID: 25554246; PMCID: PMC4320440.
  13. Satapathy S., Mittal B.R., Sood A. et al. ¹⁷⁷Lu-PSMA-617 versus docetaxel in chemotherapy- naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non- inferiority trial. Eur J Nucl Med Mol Imaging. 2022;49(5):1754-1764. doi: 10.1007/S00259-021- 05618-3/TABLES/2
  14. Hofman M.S., Emmett L., Sandhu S. et al. [¹⁷⁷Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. The Lancet. 2021;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3
  15. Fahmy O., Alhakamy N.A., Rizg W.Y. et al. Updates on Molecular and Biochemical Development and Progression of Prostate Cancer. Journal of Clinical Medicine. 2021;10(21):5127. doi: 10.3390/JCM10215127
  16. Wang J. song, Wang H. juan, Qian H. li. Biological effects of radiation on cancer cells. Mil Med Res. 2018;5(1):1–10. doi: 10.1186/S40779-018-0167-4/METRICS
  17. Di Lalla V., Elakshar S., Anidjar M. et al. Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience. Front Oncol. 2022;12. doi: 10.3389/FONC.2022.1028858
  18. Vyas M., Lim R., Fagan J., Chandrashekar R. Stability Matters: Radiochemical Stability of Therapeutic Radiopharmaceutical ¹⁷⁷Lu-PSMA I&T. J Nucl Med Technol. 2022;50(3):244–247. doi: 10.2967/JNMT.121.262423
  19. Wolf P., Freudenberg N., Bühler P. et al. Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer. Prostate. 2010;70(5):562–569. doi: 10.1002/PROS.21090
  20. Hupe M.C., Philippi C., Roth D. et al. Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis. Front Oncol. 2018;8(dec):623. doi: 10.3389/FONC.2018.00623
  21. Liu X., Fang G.C., Lu H., Shi Z.D., Chen Z.S., Han C.H. Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Drugs of Today. 2023;59(1):37. doi: 10.1358/DOT.2023.59.1.3476574
  22. Hennrich U., Eder M. ¹⁷⁷Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals. 2022;15(10). doi: 10.3390/PH15101292

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу
2. Figure 1. CONSORT diagram for the screening and selection processes of the included studies

Жүктеу (2MB)
Метадеректер
3. Figure 2. Total percentage risk of bias for all the randomized trials: green, low risk; yellow, unclear; red, high risk

Жүктеу (3MB)
Метадеректер
4. Figure 3. Risk of bias in the randomized trials: green, low risk; yellow, unclear; red, high risk

Жүктеу (3MB)
Метадеректер
5. Figure 4. Forest plot for the effect of ¹⁷⁷Lu-PSMA-617 on PSA response (a) and progression-free survival (b)

Жүктеу (5MB)
Метадеректер
6. Figure 5. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) adverse events, b) fatigue, c) pain, d) nausea e) vomiting

Жүктеу (7MB)
Метадеректер
7. Figure 6. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) diarrhoea, b) constipation, c) anaemia, d) thrombocytopenia e) leucopoenia

Жүктеу (1MB)
Метадеректер
8. Figure 7. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) dose reduction, b) discontinuation, c) mortality

Жүктеу (7MB)
Метадеректер

© Bionika Media, 2025