Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review
- PDF / 895,291 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 5 Downloads / 226 Views
REVIEW ARTICLE
Apalutamide, enzalutamide, and darolutamide for non‑metastatic castration‑resistant prostate cancer: a systematic review and network meta‑analysis Keiichiro Mori1,2 · Hadi Mostafaei1,3 · Benjamin Pradere1,4 · Reza Sari Motlagh1 · Fahad Quhal1,5 · Ekaterina Laukhtina1,6 · Victor M. Schuettfort1,7 · Mohammad Abufaraj1,8 · Pierre I. Karakiewicz9 · Takahiro Kimura2 · Shin Egawa2 · Shahrokh F. Shariat1,6,8,10,11,12,13,14 Received: 1 June 2020 / Accepted: 16 August 2020 © The Author(s) 2020
Abstract Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with nextgeneration androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/ PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials. Keywords Non-metastatic castration-resistant prostate cancer · Network meta-analysis · Apalutamide · Darolutamide · Enzalutamide
Introduction Prostate cancer is the most common solid cancer and the second most common cause of cancer-related death in men [1]. Systemic therapy based on androgen deprivation is the standard primary treatment strategy in patients with Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10147-020-01777-9) contains supplementary material, which is available to authorized users. * Shahrokh F. Shariat [email protected] Extended author information available on the last page of the article
advanced prostate cancer. Despite ad
Data Loading...
