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Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: a systematic review and meta-analysis

Prostate Cancer and Prostatic Diseases volume 23, pages 539–548 (2020)Cite this article

Subjects

Abstract

Background

This systematic review and meta-analysis aimed to assess the prognostic value of sequential of abiraterone (ABI) and enzalutamide (ENZ) therapy in patients with castration-resistant prostate cancer (CRPC).

Methods

PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched for articles published prior to December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared overall survival (OS), combined progression-free survival (PFS), combined prostate specific antigen (PSA)-PFS, and PSA response rates in CRPC patients receiving sequential ABI/ENZ or vice versa. PSA response to both the first and second agents was defined as a >50% decrease in PSA achieved with each of these agents. Formal meta-analyses were performed for these outcomes.

Results

Ten studies with 1096 patients were eligible for the systematic review and eight studies with 643 patients for the meta-analysis. The ABI-to-ENZ sequence was significantly associated with better PFS (pooled hazard ratio (HR): 0.62, 95% confidential interval (CI): 0.49–0.78, P < 0.001), and PSA–PFS (pooled HR: 0.48, 95% CI: 0.38–0.61, P < 0.001) than the ENZ-to-ABI sequence. PSA response rates of both agents were significantly better with the ABI-to-ENZ sequence (risk ratio: 0.21, 95% CI: 0.09–0.47, P < 0.001). In contrast, treatment sequence was not significantly associated with OS (pooled HR: 0.77, 95% CI: 0.59–1.01, P = 0.055).

Conclusions

ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS, PSA–PFS, and PSA response rates. Regardless of sequencing, response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy. Despite this, treatment sequencing is important to achieve the maximum possible benefit from available drugs in CRPC.

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Fig. 1: Study selection process.
Fig. 2: Forest plot (association of androgen receptor axis-targeted (ARAT) treatment sequence with oncological outcomes).
Fig. 3: Forest plot (association of androgen receptor axis-targeted (ARAT) treatment sequence with PSA response rate).

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Author information

Authors and Affiliations

  1. Department of Urology, Medical University of Vienna, Vienna, Austria

    Keiichiro Mori, Noriyoshi Miura, Hadi Mostafaei, Fahad Quhal, Reza Sari Motlagh, Benjamin Pradere, Shoji Kimura & Shahrokh F. Shariat

  2. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan

    Keiichiro Mori, Shoji Kimura, Takahiro Kimura & Shin Egawa

  3. Department of Urology, Ehime University Graduate School of Medicine, Ehime, Japan

    Noriyoshi Miura

  4. Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Hadi Mostafaei

  5. Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia

    Fahad Quhal

  6. Department of Urology, CHRU Tours, Francois Rabelais University, Tours, France

    Benjamin Pradere

  7. Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

    Alberto Briganti

  8. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada

    Pierre I. Karakiewicz

  9. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Shahrokh F. Shariat

  10. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  11. Department of Urology, University of Texas Southwestern, Dallas, TX, USA

    Shahrokh F. Shariat

  12. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

    Shahrokh F. Shariat

  13. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    Shahrokh F. Shariat

  14. Department of Urology, University of Jordan, Amman, Jordan

    Shahrokh F. Shariat

  15. European Association of Urology Research Foundation, Arnhem, Netherlands

    Shahrokh F. Shariat

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  1. Keiichiro Mori
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Contributions

Project development: KM, TK, SE, AB, PIK, and SFS. Data collection: KM and NM. Data analysis: KM and NM. Manuscript writing/editing: KM, NM, HM, FQ, RSM, BP, SK, TK, SE, AB, PIK, and SFS.

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Correspondence to Shahrokh F. Shariat.

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Mori, K., Miura, N., Mostafaei, H. et al. Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 23, 539–548 (2020). https://doi.org/10.1038/s41391-020-0222-6

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