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Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients

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Abstract

Background and Objectives

Several systemic treatments are available for metastatic hormone sensitive prostate cancer (mHSPC) including docetaxel (D), abiraterone and prednisone (A + P) and new anti-androgens (NA). In our study we performed a systematic review and meta-analysis assessing efficacy outcomes (survival and radiological-free survival), safety and survival on specific subgroups of patients.

Methods

Outcomes of interest were: (i) Risk of death, biochemical and radiological progression among all patients. (ii) Risk of death according to different pathological/clinical features. (iii) Evaluation of the relative risk (RR) and risk difference of serious toxicity defined as adverse events (AEs) with grade ≥ 3 specific AEs. Hazard ratios (HRs) and RR were measures adopted for endpoints 1–3.

Results

Overall, eight randomized trials were included in meta-analysis for a total of 9987 patients. Administration of D, A + P and NA resulted in improved overall survival (OS) and radiological progression-free survival (rPFS). Survival benefit was not confirmed in patients receiving NA and previously exposed to docetaxel (HR 0.948, 95% CI 0.671–1.338). Patients with visceral metastases and high lactate dehydrogenase (LDH) did not benefit from NA treatment, while it seems that patients with low Gleason score do not benefit from A + P. NA showed the more favorable safety profile.

Conclusion

NA may not provide survival benefit when adopted subsequently or in concomitant to D. Specific subgroups of patients may benefit more from A + P, D or NA. Safety profiles significantly differ among agents evaluated.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551.

    Article  PubMed  Google Scholar 

  2. Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis. 2016;19:395–7.

    Article  CAS  PubMed  Google Scholar 

  3. C. Mosillo, R. Iacovelli, C. Ciccarese, Fantinel E, Bimbatti D, Brunelli M et al. De novo metastatic castration sensitive prostate cancer: state of art and future perspectives Cancer Treat Rev. 2018; 70:67–74. https://doi.org/10.1016/j.ctrv.2018.08.005.

    Article  PubMed  Google Scholar 

  4. Iacovelli R, Ciccarese C, Mosillo C, Bimbatti D, Fantinel E, Stefani L, et al. Comparison between prognostic classifications in de novo metastatic hormone sensitive prostate cancer. Target Oncol. 2018;13(5):649–55. https://doi.org/10.1007/s11523-018-0588-8.

    Article  PubMed  Google Scholar 

  5. Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(2):149–58. https://doi.org/10.1016/S1470-2045(12)70560-0.

    Article  CAS  PubMed  Google Scholar 

  6. Gravis G, Boher JM, Joly F, Soulié M, Albiges L, Latorzeff I, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70(2):256–62. https://doi.org/10.1016/j.eururo.2015.11.005.

    Article  CAS  PubMed  Google Scholar 

  7. 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(8):737–46. https://doi.org/10.1056/NEJMoa1503747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemo-hormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080–7. https://doi.org/10.1200/JCO.2017.75.3657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. James ND, Sydes MR, Clarke NW, Mason MD, Daernaley DP, Spears MR, et al. 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;387(10024):1163–77. https://doi.org/10.1016/S0140-6736(15)01037-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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(4):352–60. https://doi.org/10.1056/NEJMoa1704174.

    Article  CAS  PubMed  Google Scholar 

  11. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Daernaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338–51. https://doi.org/10.1056/NEJMoa1702900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13–24. https://doi.org/10.1056/nejmoa1903307.

    Article  CAS  PubMed  Google Scholar 

  13. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121–31. https://doi.org/10.1056/NEJMoa1903835.

    Article  PubMed  Google Scholar 

  14. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A et al. ARCHES: A randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;22:JCO1900799. https://doi.org/10.1200/jco.19.00799.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Marchioni M, Di Nicola M, Primiceri G, Novara G, Castellan P, Paul A et al. New anti-androgen compounds compared to docetaxel in metastatic hormone sensitive prostate cancer: results from a network meta-analysis. J Urol. 2019. https://doi.org/10.1097/ju.0000000000000636.

  16. Sathianathen NJ, Koschel S, Thangasamy IA, Teh J, Alghazo O, Butcher G, et al. Indirect comparisons of efficacy between combination approaches in metastatic hormone-sensitive prostate cancer: a systematic review and network meta-analysis. Eur Urol. 2019. https://doi.org/10.1016/j.eururo.2019.09.004.

    Article  PubMed  Google Scholar 

  17. Higgins JP, Altman DG, Gøtzsche PC, Gotzsche PC, Juni P, Moher D et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Altman DG, Machin D, Bryant TN, and Gardner MJ. Statistics with confidence, second edition. British Medical Journal London; 2000, pp. 45–56.

  19. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester: Wiley; 2009.

    Book  Google Scholar 

  20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yates F. Contingency table involving small numbers and the x2 test. J R Stat Soc. 1934;1:217–35.

    Google Scholar 

  23. Wallis CJD, Klaassen Z, Bhindi B, Goldberg H, Chandrasekar T, Farrell AM, et al. Comparison of abiraterone acetate and docetaxel with androgen deprivation therapy in high-risk and metastatic hormone-naïve prostate cancer: a systematic review and network meta-analysis. Eur Urol. 2018;73(6):834–44. https://doi.org/10.1016/j.eururo.2017.10.002.

    Article  CAS  PubMed  Google Scholar 

  24. Vale CL, Fisher DJ, White IR, Carpenter JR, Burdett S, Clarke NW, et al. What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis. Ann Oncol. 2018;29(5):1249–57. https://doi.org/10.1093/annonc/mdy071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Feyerabend S, Saad F, Li T, Ito T, Diels J, Van Sanden S, et al. Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: a network meta-analysis. Eur J Cancer. 2018;103:78–87. https://doi.org/10.1016/j.ejca.2018.08.010.

    Article  CAS  PubMed  Google Scholar 

  26. Iacovelli R, Ciccarese C, Bria E, Romano M, Fantinel E, Bimbatti D et al. The cardiovascular toxicity of abiraterone and enzalutamide in prostate cancer. Clin Genitourin Cancer 2018;16(3):e645–e653. https://doi.org/10.1016/j.clgc.2017.12.007(epub 2017 Dec 27).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy

    Vincenzo Di Nunno, Veronica Mollica, Andrea Ardizzoni & Francesco Massari

  2. Oncology Unit, Macerata Hospital, Macerata, Italy

    Matteo Santoni & Nicola Battelli

  3. Azienda Ospedaliera dell’Alto Adige, Bressanone/Brixen Hospital, Bressanone, Italy

    Alessandro Conti

  4. Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy

    Rodolfo Montironi

Authors
  1. Vincenzo Di Nunno
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  2. Matteo Santoni
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Correspondence to Francesco Massari.

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Di Nunno, V., Santoni, M., Mollica, V. et al. Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients. Clin Drug Investig 40, 211–226 (2020). https://doi.org/10.1007/s40261-020-00888-5

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  • DOI: https://doi.org/10.1007/s40261-020-00888-5

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