TY - JOUR
T1 - Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer
T2 - Results from the Dutch Castration-resistant Prostate Cancer Registry
AU - Kuppen, Malou C P
AU - Westgeest, Hans M
AU - van den Eertwegh, Alphonsus J M
AU - van Moorselaar, Reindert J A
AU - van Oort, Inge M
AU - Coenen, Juleon L L M
AU - van den Bergh, A C M Fons
AU - Mehra, Niven
AU - Somford, Diederik M
AU - Bergman, Andre M
AU - Ten Bokkel Huinink, Daan
AU - Fossion, Laurent
AU - Geenen, Maud M
AU - Hendriks, Mathijs P
AU - van de Luijtgaarden, Addy C M
AU - Polee, Marco B
AU - Weijl, Nir I
AU - van de Wouw, Agnes J
AU - de Wit, Ronald
AU - Uyl-de Groot, Carin A
AU - Gerritsen, Winald R
N1 - Publisher Copyright: Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2).OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2.DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed.RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research.CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P.PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.
AB - BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2).OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2.DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed.RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research.CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P.PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.
KW - Abiraterone acetate
KW - Androgen-receptor targeting agents
KW - Castration-resistant prostate cancer
KW - Cross resistance
KW - Enzalutamide
KW - Real-world outcomes
KW - Sequencing
UR - http://www.scopus.com/inward/record.url?scp=85114120021&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.euo.2019.09.005
DO - https://doi.org/10.1016/j.euo.2019.09.005
M3 - Article
C2 - 31601523
SN - 2588-9311
VL - 4
SP - 618
EP - 627
JO - European Urology Oncology
JF - European Urology Oncology
IS - 4
ER -