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.

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

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology CHRU Tours Francois Rabelais University Tours France

Department of Urology Ehime University Graduate School of Medicine Ehime Japan

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Jordan Amman Jordan

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

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

European Association of Urology Research Foundation Arnhem Netherlands

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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

Zobrazit více v PubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: a cancer J clinicians. 2018;68:7–30.

Kluth LA, Shariat SF, Kratzik C, Tagawa S, Sonpavde G, Rieken M, et al. The hypothalamic-pituitary-gonadal axis and prostate cancer: implications for androgen deprivation therapy. World J Urol. 2014;32:669–76. DOI

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. DOI

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. DOI

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. DOI

Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33. DOI

Oh WK, Cheng WY, Miao R, Vekeman F, Gauthier-Loiselle M, Duh MS, et al. Real-world outcomes in patients with metastatic castration-resistant prostate cancer receiving second-line chemotherapy versus an alternative androgen receptor-targeted agent (ARTA) following early progression on a first-line ARTA in a US community oncology setting. Urol Oncol. 2018;36:500.e501–500.e509. DOI

Chi K, Hotte SJ, Joshua AM, North S, Wyatt AW, Collins LL, et al. Treatment of mCRPC in the AR-axis-targeted therapy-resistant state. Ann Oncol: Off J Eur Soc Med Oncol. 2015;26:2044–56. DOI

Maughan BL, Luber B, Nadal R, Antonarakis ES. Comparing sequencing of abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer: a retrospective study. Prostate. 2017;77:33–40. DOI

Mori K, Kimura T, Onuma H, Kimura S, Yamamoto T, Sasaki H, et al. Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer. Prostate. 2017;77:1144–50. DOI

Miyake H, Hara T, Tamura K, Sugiyama T, Furuse H, Ozono S, et al. Comparative assessment of efficacies between 2 alternative therapeutic sequences with novel androgen receptor-axis-targeted agents in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Clin Genitourin cancer. 2017;15:e591–7. DOI

Terada N, Maughan BL, Akamatsu S, Kobayashi T, Yamasaki T, Inoue T, et al. Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy-naive castration-resistant prostate cancer: the Kyoto-Baltimore collaboration. Int J Urol: Off J Jpn Urological Assoc. 2017;24:441–8. DOI

Matsubara N, Yamada Y, Tabata K, Satoh T, Kamiya N, Suzuki H, et al. Abiraterone followed by enzalutamide versus enzalutamide followed by abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2018;16:142–8. DOI

Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW, et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018;8:444–57. DOI

Khalaf DJ, Annala M, Taavitsainen S, Finch DL, Oja C, Vergidis J, et al. Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Lancet Oncol. 2019;20:1730–9. DOI

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. PLoS Med. 2009;6:e1000100. DOI

Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. DOI

Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, et al. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7:1–173. DOI

Altman DG, Bland JM. How to obtain the confidence interval from a P value. BMJ (Clin Res ed). 2011;343:d2090. DOI

Altman DG, Bland JM. How to obtain the P value from a confidence interval. BMJ (Clin Res ed). 2011;343:d2304. DOI

DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin trials. 2007;28:105–14. DOI

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

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clin Res ed). 2003;327:557–60. DOI

Sterne JAC, Harbord RM. Funnel plots in meta-analysis. Stata J. 2004;4:127–41. DOI

Miyamae K, Kitani K, Hara K, Nakakuma K, Hamada S, Hamada Y. Clinical study of sequential therapy with abiraterone and enzalutamide following docetaxel therapy for castration-resistant prostate cancer. Jpn J Urol. 2018;108:74–79. DOI

Komura K, Fujiwara Y, Uchimoto T, Saito K, Tanda N, Matsunaga T, et al. Comparison of radiographic progression-free survival and PSA response on sequential treatment using abiraterone and enzalutamide for newly diagnosed castration-resistant prostate cancer: a propensity score matched analysis from multicenter cohort. J Clin Med. 2019;8.

Kobayashi T, Terada N, Kimura T, Matsubara N, Murakami K, Mori K, et al. Sequential use of androgen receptor axis-targeted agents in chemotherapy-naive castration-resistant prostate cancer: a multicenter retrospective analysis with 3-Year follow-up. Clin Genitourin Cancer. 2020;18:e46–54. DOI

Okita K, Hatakeyama S, Narita S, Takahashi M, Sakurai T, Kawamura S, et al. The effect of treatment sequence on overall survival for men with metastatic castration-resistant prostate cancer: a multicenter retrospective study. Clin Genitourin Cancer. 2019. [Epub ahead of print].

Efstathiou E, Titus M, Tsavachidou D, Tzelepi V, Wen S, Hoang A, et al. Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. J Clin Oncol: Off J Am Soc Clin Oncol. 2012;30:637–43. DOI

Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015;67:53–60. DOI

de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, et al. Cabazitaxel versus Abiraterone or Enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381:2506–18. DOI