Highlights
- •Efficacy assessment of treatment sequences based on AAP and ENZ in mCRPC patients.
- •AAP-ENZ sequence showed a statistically significant longer PSA-PFS than ENZ-AAP.
- •Literature revealed favourable results in terms of PFS and PSA levels for AAP-ENZ.
- •Clinical efficacy of AAP administered as the first-line treatment in mCRPC patients.
Abstract
Purpose
To evaluate the impact of the hormonal treatment sequencing including abiraterone
acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which
sequence provides more benefits for patients.
Methods
Studies published in English between 1 January 2013 and 30 September 2017 were identified
in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment
sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis.
Results
Seventeen studies met the inclusion criteria. Two assessed both treatment sequences
AAP → ENZ and ENZ → AAP; it was found that sequence of AAP → ENZ showed a statistically
significantly longer PSA-PFS than the observed in ENZ → AAP (pooled HR: 0,54; 95%
CI; 0,36–0,82; p < 0,05). The nine studies analysing Doc → AAP → ENZ sequence, revealed favourable results
in terms of PFS. The 5 studies which analysed AAP → ENZ sequence, show a decrease
in PSA levels ≥ 50% in 11–41% of patients treated with enzalutamide after previous
treatment with AAP. In the two studies that analysed the Doc → ENZ → AAP sequence,
PSA response rates were much lower than those reported with Doc → AAP → ENZ, with
decreases in PSA ≥ 30 of 3–18% and PSA ≥ 50 of 8–11%.
Conclusion
Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC
patients followed by enzalutamide, delaying disease progression, compared with the
ENZ → AAP sequence. However, more studies and randomized trials are needed, to validate
the best treatment sequencing.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Cancer Treatment ReviewsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epidemiology of Prostate Cancer.World J Oncol. 2019; 10: 63-89https://doi.org/10.14740/wjon1191
- Prostate cancer in elderly men.Rev Urol. 2008; 10: 111-119
- Steps in prostate cancer progression that lead to bone metastasis.Int J Cancer. 2011; 128: 2545-2561https://doi.org/10.1002/ijc.26024
- A population-based study of progression to metastatic prostate cancer in Australia.Cancer Epidemiol. 2015; 39: 617-622https://doi.org/10.1016/j.canep.2015.04.013
- Prostate cancer in the elderly: frequency of advanced disease at presentation and disease-specific mortality.Cancer. 2012; 118: 3062-3070https://doi.org/10.1002/cncr.26392
- Risk profiles of prostate cancers identified from UK primary care using national referral guidelines.Br J Cancer. 2012; 106: 436-439https://doi.org/10.1038/bjc.2011.596
- Guidelines for the management of castrate-resistant prostate cancer.Can Urol Assoc J. 2010; 4: 380-384https://doi.org/10.5489/cuaj.10167
- Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.J Clin Oncol. 2008; 26: 1148-1159https://doi.org/10.1200/jco.2007.12.4487
- Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.N Engl J Med. 2004; 351: 1502-1512https://doi.org/10.1056/NEJMoa040720
- Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.Lancet. 2010; 376: 1147-1154https://doi.org/10.1016/s0140-6736(10)61389-x
- Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study.Lancet Oncol. 2012; 13: 983-992https://doi.org/10.1016/s1470-2045(12)70379-0
- Sipuleucel-T immunotherapy for castration-resistant prostate cancer.N Engl J Med. 2010; 363: 411-422https://doi.org/10.1056/NEJMoa1001294
- Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial.Lancet Oncol. 2015; 16: 509-521https://doi.org/10.1016/s1470-2045(15)70113-0
- Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results.J Clin Oncol. 2015; 33: 1356-1363https://doi.org/10.1200/jco.2014.55.3875
- Alpha emitter radium-223 and survival in metastatic prostate cancer.N Engl J Med. 2013; 369: 213-223https://doi.org/10.1056/NEJMoa1213755
- Increased survival with enzalutamide in prostate cancer after chemotherapy.N Engl J Med. 2012; 367: 1187-1197https://doi.org/10.1056/NEJMoa1207506
- Systematic Review of Efficacy and Health Economic Implications of Real-world Treatment Sequencing in Prostate Cancer: Where Do the Newer Agents Enzalutamide and Abiraterone Fit in?.Eur Urol Focus. 2020; https://doi.org/10.1016/j.euf.2020.03.003
- Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.N Engl J Med. 2018; 378: 1408-1418https://doi.org/10.1056/NEJMoa1715546
- Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer.N Engl J Med. 2018; 378: 2465-2474https://doi.org/10.1056/NEJMoa1800536
- Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer.N Engl J Med. 2019; 380: 1235-1246https://doi.org/10.1056/NEJMoa1815671
EPAR-Erleada-EMA/CHMP/3945/2020. In. https://www.ema.europa.eu/en/documents/variation-report/erleada-h-c-4452-ii-0001-epar-assessment-report-variation_en-0.pdf.
EPAR-Nubeqa-EMA/84124/2020. In. https://www.ema.europa.eu/en/documents/assessment-report/nubeqa-epar-public-assessment-report_en.pdf.
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.PLoS Med. 2009; 6e1000100https://doi.org/10.1371/journal.pmed.1000100
- GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926https://doi.org/10.1136/bmj.39489.470347.AD
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560https://doi.org/10.1136/bmj.327.7414.557
- Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.Prostate. 2017; 77: 1144-1150https://doi.org/10.1002/pros.23373
- Comparing Sequencing of Abiraterone and Enzalutamide in Men With Metastatic Castration-Resistant Prostate Cancer: A Retrospective Study.Prostate. 2017; 77: 33-40https://doi.org/10.1002/pros.23246
- Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients.Eur Urol. 2015; 67: 23-29https://doi.org/10.1016/j.eururo.2014.06.045
- Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment.Cancer. 2014; 120: 968-975https://doi.org/10.1002/cncr.28518
- Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation.Prostate. 2016; 76: 32-40https://doi.org/10.1002/pros.23094
- Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone.Eur J Cancer. 2014; 50: 78-84https://doi.org/10.1016/j.ejca.2013.08.020
- Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis.Eur Urol. 2015; 68: 317-324https://doi.org/10.1016/j.eururo.2014.07.028
- Activity of enzalutamide in men with metastatic castration-resistant prostate cancer is affected by prior treatment with abiraterone and/or docetaxel.Prostate Cancer Prostatic Dis. 2015; 18: 122-127https://doi.org/10.1038/pcan.2014.53
- Third-line Enzalutamide Following Docetaxel and Abiraterone in Metastatic Castrate-resistant Prostate Cancer.Anticancer Res. 2016; 36: 1799-1803
- Enzalutamide after docetaxel and abiraterone therapy in metastatic castration-resistant prostate cancer.Adv Ther. 2014; 31: 234-241https://doi.org/10.1007/s12325-014-0092-1
- Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone.Eur Urol. 2014; 65: 30-36https://doi.org/10.1016/j.eururo.2013.06.042
- Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate.Scand J Urol. 2014; 48: 268-275https://doi.org/10.3109/21681805.2013.860189
- Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer.Clin Genitourin Cancer. 2015; 13: 392-399https://doi.org/10.1016/j.clgc.2015.01.004
- Efficacy and safety of enzalutamide (ENZA) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate (Abi): A multicenter, single-arm, open-label study.J Clin Oncol. 2017; 35https://doi.org/10.1200/JCO.2017.35.6_suppl.165
- Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone.Prostate. 2014; 74: 1278-1285https://doi.org/10.1002/pros.22844
- Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100).Ann Oncol. 2013; 24: 1807-1812https://doi.org/10.1093/annonc/mdt136
- Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide.Ann Oncol. 2013; 24: 1802-1807https://doi.org/10.1093/annonc/mdt138
- 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: 1730-1739https://doi.org/10.1016/s1470-2045(19)30688-6
- AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.N Engl J Med. 2014; 371: 1028-1038https://doi.org/10.1056/NEJMoa1315815
- Understanding the mechanisms of androgen deprivation resistance in prostate cancer at the molecular level.Eur Urol. 2015; 67: 470-479https://doi.org/10.1016/j.eururo.2014.09.049
- Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines.Cancer Res. 2013; 73: 483-489https://doi.org/10.1158/0008-5472.Can-12-3630
- Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer.Clin Cancer Res. 2015; 21: 2315-2324https://doi.org/10.1158/1078-0432.Ccr-14-2666
- Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.Cancer Res. 2011; 71: 6503-6513https://doi.org/10.1158/0008-5472.Can-11-0532
- Overcoming mutation-based resistance to antiandrogens with rational drug design.Elife. 2013; 2e00499https://doi.org/10.7554/eLife.00499
- A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509.Cancer Discov. 2013; 3: 1020-1029https://doi.org/10.1158/2159-8290.Cd-13-0226
- Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade.Cell. 2013; 155: 1309-1322https://doi.org/10.1016/j.cell.2013.11.012
- The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy.Clin Cancer Res. 2018; 24: 927-938https://doi.org/10.1158/1078-0432.Ccr-17-0989
- Cross-resistance between taxanes and new hormonal agents abiraterone and enzalutamide may affect drug sequence choices in metastatic castration-resistant prostate cancer.Eur J Cancer. 2013; 49: 3821-3830https://doi.org/10.1016/j.ejca.2013.09.026
- Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer.Cancer Cell. 2011; 19: 575-586https://doi.org/10.1016/j.ccr.2011.04.008
- Synergistic targeting of PI3K/AKT pathway and androgen receptor axis significantly delays castration-resistant prostate cancer progression in vivo.Mol Cancer Ther. 2013; 12: 2342-2355https://doi.org/10.1158/1535-7163.Mct-13-0032
- What do we know about treatment sequencing of abiraterone, enzalutamide, and chemotherapy in metastatic castration-resistant prostate cancer?.World J Urol. 2016; 34: 617-624https://doi.org/10.1007/s00345-015-1687-0
- Enzalutamide after docetaxel and abiraterone acetate treatment in prostate cancer: a pooled analysis of 10 case series.Clin Genitourin Cancer. 2015; 13: 193-198https://doi.org/10.1016/j.clgc.2014.10.006
Chung DY, Kang DH, Kim JW et al. Comparison of Oncologic Outcomes Between Two Alternative Sequences with Abiraterone Acetate and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2019; 12: DOI: 10.3390/cancers12010008.
Article Info
Publication History
Published online: January 11, 2021
Accepted:
December 24,
2020
Received in revised form:
December 22,
2020
Received:
October 21,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
