Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis
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Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis. / Mori, Keiichiro; Mostafaei, Hadi; Pradere, Benjamin; Motlagh, Reza Sari; Quhal, Fahad; Laukhtina, Ekaterina; Schuettfort, Victor M; Abufaraj, Mohammad; Karakiewicz, Pierre I; Kimura, Takahiro; Egawa, Shin; Shariat, Shahrokh F.
in: INT J CLIN ONCOL, Jahrgang 25, Nr. 11, 11.2020, S. 1892-1900.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis
AU - Mori, Keiichiro
AU - Mostafaei, Hadi
AU - Pradere, Benjamin
AU - Motlagh, Reza Sari
AU - Quhal, Fahad
AU - Laukhtina, Ekaterina
AU - Schuettfort, Victor M
AU - Abufaraj, Mohammad
AU - Karakiewicz, Pierre I
AU - Kimura, Takahiro
AU - Egawa, Shin
AU - Shariat, Shahrokh F
PY - 2020/11
Y1 - 2020/11
N2 - Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation 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.
AB - Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation 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.
KW - Androgen Receptor Antagonists/therapeutic use
KW - Antineoplastic Agents/therapeutic use
KW - Humans
KW - Kallikreins/metabolism
KW - Male
KW - Network Meta-Analysis
KW - Phenylthiohydantoin/analogs & derivatives
KW - Progression-Free Survival
KW - Proportional Hazards Models
KW - Prostate-Specific Antigen/metabolism
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
KW - Pyrazoles/therapeutic use
KW - Thiohydantoins/therapeutic use
KW - Treatment Outcome
U2 - 10.1007/s10147-020-01777-9
DO - 10.1007/s10147-020-01777-9
M3 - SCORING: Journal article
C2 - 32924096
VL - 25
SP - 1892
EP - 1900
JO - INT J CLIN ONCOL
JF - INT J CLIN ONCOL
SN - 1341-9625
IS - 11
ER -
