Highlights
- •The optimal therapeutic sequence for mCRPC is unclear.
- •There is no difference in OS/PFS between first-line abiraterone and enzalutamide.
- •In second line, docetaxel is better than androgen-receptor therapy.
- •Efforts must be made to better select the optimal first- and second-line treatments.
Abstract
Background
The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer
(mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus
that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line
ART.
Patients and Methods
This retrospective study included all consecutive chemo-naive mCRPC patients who have
received first-line ART treatment. Progression-free survival (PFS) and overall survival
(OS) were compared between patients treated with second-line ART or TAX.
Results
Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone
(ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received
second-line TAX and ART, respectively, while 76 (43%) patients did not receive further
treatment. From the start of first-line therapy, the median PFS and OS were 13 months
(95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant
difference between ENZA and ABI. From the start of second-line therapy, the median
PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively.
Compared with ART, docetaxel was associated with significantly higher prostate-specific
antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95%
CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months,
P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART.
Conclusion
In the second-line setting, TAX provides higher PSA and radiological responses than
does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar.
This study provides new elements to help deciding the best treatment sequence.
Keywords
Abbreviations:
ABI (abiraterone), ART (androgen-receptor therapy), ECOG-PS (Eastern Cooperative Oncology Group Performance Status), ENZA (enzalutamide), mCRPC (metastatic castrate-resistance prostate cancer), OS (overall survival), PARP (poly(ADP-ribose) polymerase), PFS (progression-free survival), PSA (prostate-specific antigen), TAX (taxanes)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 Clinical Genitourinary CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018; 68: 394-424
- Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.N Engl J Med. 2004; 351: 1502-1512
- Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.Lancet. 2010; 376: 1147-1154
- Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial-FIRSTANA.J Clin Oncol. 2017; 35: 3189-3197
- 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: 983-992
- Abiraterone in metastatic prostate cancer without previous chemotherapy.N Engl J Med. 2013; 368: 138-148
- Increased survival with enzalutamide in prostate cancer after chemotherapy.N Engl J Med. 2012; 367: 1187-1197
- Enzalutamide in metastatic prostate cancer before chemotherapy.N Engl J Med. 2014; 371: 424-433
- Sipuleucel-T immunotherapy for castration-resistant prostate cancer.N Engl J Med. 2010; 363: 411-422
- Alpha emitter radium-223 and survival in metastatic prostate cancer.N Engl J Med. 2013; 369: 213-223
- Olaparib for metastatic castration-resistant prostate cancer.N Engl J Med. 2020; 382: 2091-2102
- Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer.N Engl J Med. 2021; 385: 1091-1103
- Clinical outcomes from androgen signaling-directed therapy after treatment with abiraterone acetate and prednisone in patients with metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-302.Eur Urol. 2017; 72: 10-13
- 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: 78-84
- Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients.Eur Urol. 2015; 67: 23-29
- Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe.Eur Urol. 2018; 74: 37-45
- Exploring the optimal sequence of abiraterone and enzalutamide in patients with chemotherapy-naïve castration-resistant prostate cancer: the Kyoto-Baltimore collaboration.Int J Urol. 2017; 24: 441-448
- Comparing sequencing of abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer: a retrospective study.Prostate. 2017; 77: 33-40
- Abiraterone followed by enzalutamide versus enzalutamide followed by abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.Clin Genitourin Cancer. 2018; 16: 142-148
- Management of patients with advanced prostate cancer: the report of the advanced prostate cancer consensus conference APCCC 2017.Eur Urol. 2018; 73: 178-211
- Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone.Prostate. 2014; 74: 1278-1285
- Sequencing of cabazitaxel and abiraterone acetate after docetaxel in metastatic castration-resistant prostate cancer: treatment patterns and clinical outcomes in multicenter community-based US oncology practices.Clin Genitourin Cancer. 2015; 13: 309-318
- Results of the FLAC European database of metastatic castration-resistant prostate cancer patients treated with docetaxel, cabazitaxel, and androgen receptor-targeted agents.Clin Genitourin Cancer. 2018; 16: e777-e784
- Sequencing of taxanes and new androgen-targeted therapies in metastatic castration-resistant prostate cancer: results of the international multicentre retrospective CATS database.Eur Urol Oncol. 2018; 1: 467-475
- Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer.N Engl J Med. 2019; 381: 2506-2518
- Controlling the control arm in metastatic castration-resistant prostate cancer trials: best standard of care or the minimum standard of care?.J Clin Oncol. 2022; 40: 1518-1521
- 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: 1730-1739
Article info
Publication history
Published online: February 16, 2023
Accepted:
February 13,
2023
Received in revised form:
February 9,
2023
Received:
August 30,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.