Androgen annihilation versus advanced androgen blockage as first line treatment for metastatic castration resistant prostate cancer: A systematic review and meta-analysis.
Abiraterone
Androgen annihilation
Enzalutamide
MCRPC
Novel hormonal therapy
Overall survival
Progression free survival
Journal
Critical reviews in oncology/hematology
ISSN: 1879-0461
Titre abrégé: Crit Rev Oncol Hematol
Pays: Netherlands
ID NLM: 8916049
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
18
05
2022
revised:
26
07
2022
accepted:
23
08
2022
pubmed:
29
8
2022
medline:
18
10
2022
entrez:
28
8
2022
Statut:
ppublish
Résumé
Despite recent advances in the treatments of metastatic castration resistant prostate cancer (mCRPC), patients' prognosis remains suboptimal and novel treatment combinations are under scrutiny. On this matter, the recent ACIS trial tested the role of abiraterone plus apalutamide (androgen annihilation) in addition to androgen deprivation therapy, versus abiraterone plus androgen deprivation therapy. Herein, we performed a meta-analysis to compare overall survival (OS) and progression free survival (PFS) among patients who received androgen annihilation versus advanced androgen blockage (abiraterone or enzalutamide), in addition to conventional androgen deprivation therapy. A comprehensive search for all published phase III randomized control trials on first line mCRPC that evaluated advanced androgen blockage (COU-AA-302, PREVAIL) or androgen annihilation (ACIS) was conducted PubMed, EMBASE, Web of Science, and Scopus databases up to 31/12/2021. We reconstructed survival data from published Kaplan-Meier curves on overall survival (OS) and progression free survival (PFS) and meta-analyzed androgen annihilation versus advanced androgen blockage (grouping together abiraterone and enzalutamide) versus androgen deprivation therapy. The outcomes of interest were assessed using difference in restricted mean survival time (ΔRMST) at different time points. Three trials were included involving 3787 patients. Overall, patients receiving androgen annihilation exhibited similar OS compared to advanced androgen blockage: ΔRMST at 36 months of - 0.2 (95%CI: -1.1, 0.8, p = 0.8). At 36 months, relatively to ADT alone, patients receiving androgen annihilation or advanced androgen blockage exhibited longer OS: ΔRMST of 1.6 (95%CI: 0.6, 2.7, p = 0.002) and 1.8 months (95%CI: 1.1, 2.5, p < 0.001), respectively. Patients receiving androgen annihilation exhibited better PFS compared to advanced androgen blockage: ΔRMST at 36 months of 2.4 months (95%CI: 1.0, 3.8, p = 0.001). We found no OS benefit for patients with mCRPC treated with androgen annihilation compared to advanced androgen blockage. This might be ascribed to an increased rate of other cause mortality that might determine the absence of an OS benefit or to the efficacy of second line therapies. Optimal treatment sequence and patient selection for androgen annihilation remain open points. However, a PFS benefit was found in case of combination therapy, whose clinical meaning is not yet clear.
Sections du résumé
BACKGROUND
BACKGROUND
Despite recent advances in the treatments of metastatic castration resistant prostate cancer (mCRPC), patients' prognosis remains suboptimal and novel treatment combinations are under scrutiny. On this matter, the recent ACIS trial tested the role of abiraterone plus apalutamide (androgen annihilation) in addition to androgen deprivation therapy, versus abiraterone plus androgen deprivation therapy. Herein, we performed a meta-analysis to compare overall survival (OS) and progression free survival (PFS) among patients who received androgen annihilation versus advanced androgen blockage (abiraterone or enzalutamide), in addition to conventional androgen deprivation therapy.
METHODS
METHODS
A comprehensive search for all published phase III randomized control trials on first line mCRPC that evaluated advanced androgen blockage (COU-AA-302, PREVAIL) or androgen annihilation (ACIS) was conducted PubMed, EMBASE, Web of Science, and Scopus databases up to 31/12/2021. We reconstructed survival data from published Kaplan-Meier curves on overall survival (OS) and progression free survival (PFS) and meta-analyzed androgen annihilation versus advanced androgen blockage (grouping together abiraterone and enzalutamide) versus androgen deprivation therapy. The outcomes of interest were assessed using difference in restricted mean survival time (ΔRMST) at different time points.
RESULTS
RESULTS
Three trials were included involving 3787 patients. Overall, patients receiving androgen annihilation exhibited similar OS compared to advanced androgen blockage: ΔRMST at 36 months of - 0.2 (95%CI: -1.1, 0.8, p = 0.8). At 36 months, relatively to ADT alone, patients receiving androgen annihilation or advanced androgen blockage exhibited longer OS: ΔRMST of 1.6 (95%CI: 0.6, 2.7, p = 0.002) and 1.8 months (95%CI: 1.1, 2.5, p < 0.001), respectively. Patients receiving androgen annihilation exhibited better PFS compared to advanced androgen blockage: ΔRMST at 36 months of 2.4 months (95%CI: 1.0, 3.8, p = 0.001).
CONCLUSION
CONCLUSIONS
We found no OS benefit for patients with mCRPC treated with androgen annihilation compared to advanced androgen blockage. This might be ascribed to an increased rate of other cause mortality that might determine the absence of an OS benefit or to the efficacy of second line therapies. Optimal treatment sequence and patient selection for androgen annihilation remain open points. However, a PFS benefit was found in case of combination therapy, whose clinical meaning is not yet clear.
Identifiants
pubmed: 36031173
pii: S1040-8428(22)00225-6
doi: 10.1016/j.critrevonc.2022.103801
pii:
doi:
Substances chimiques
Androgen Antagonists
0
Androgens
0
Benzamides
0
Nitriles
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Types de publication
Journal Article
Meta-Analysis
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
103801Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.