Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry

Malou C P Kuppen; Hans M Westgeest; Alphonsus J M van den Eertwegh; Reindert J A van Moorselaar; Inge M van Oort; Juleon L L M Coenen; A C M Fons van den Bergh; Niven Mehra; Diederik M Somford; Andre M Bergman; Daan Ten Bokkel Huinink; Laurent Fossion; Maud M Geenen; Mathijs P Hendriks; Addy C M van de Luijtgaarden; Marco B Polee; Nir I Weijl; Agnes J van de Wouw; Ronald de Wit; Carin A Uyl-de Groot; Winald R Gerritsen

doi:10.1016/j.euo.2019.09.005

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry

Malou C P Kuppen
, Hans M Westgeest
, Alphonsus J M van den Eertwegh
, Reindert J A van Moorselaar
, Inge M van Oort
, Juleon L L M Coenen
, A C M Fons van den Bergh
, Niven Mehra
, Diederik M Somford
, Andre M Bergman
, Daan Ten Bokkel Huinink
, Laurent Fossion
, Maud M Geenen
, Mathijs P Hendriks
, Addy C M van de Luijtgaarden
, Marco B Polee
, Nir I Weijl
, Agnes J van de Wouw
, Ronald de Wit
, Carin A Uyl-de Groot

Winald R Gerritsen

Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Rotterdam, The Netherlands. Electronic address: [email protected].
Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands. [email protected].
Department of Urology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Department of Internal Medicine and Infectious Diseases, Isala Klinieken, Zwolle, The Netherlands.
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Medical University of Vienna, Vienna, Austria.
Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Urology, Canisius Wilhemina Hospital, Nijmegen, The Netherlands.
Department of Internal Medicine, Diakonessenhuis, Utrecht, The Netherlands.
Department of Urology, Maxima Medical Center, Eindhoven, The Netherlands.
Department of Internal Medicine, OLVG, Amsterdam, The Netherlands. [email protected]
Department of Internal Medicine, Northwest Clinics, Alkmaar, The Netherlands.
Department of Internal Medicine, Reinier de Graaf Groep, Delft, The Netherlands.
From the *Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen; †Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden; Departments of ‡Nuclear Medicine and Molecular Imaging, and §Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Internal Medicine, MCH-Bronovo Hospital, 's-Gravenhage, The Netherlands.
Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands.
Department of Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Rotterdam, The Netherlands.

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Abstract

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.

Original language	English
Pages (from-to)	618-627
Number of pages	10
Journal	European Urology Oncology
Volume	4
Issue number	4
Early online date	7 Oct 2019
DOIs	https://doi.org/10.1016/j.euo.2019.09.005
Publication status	Published - 1 Aug 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Abiraterone acetate
Androgen-receptor targeting agents
Castration-resistant prostate cancer
Cross resistance
Enzalutamide
Real-world outcomes
Sequencing

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Kuppen, M. C. P., Westgeest, H. M., van den Eertwegh, A. J. M., van Moorselaar, R. J. A., van Oort, I. M., Coenen, J. L. L. M., van den Bergh, A. C. M. F., Mehra, N., Somford, D. M., Bergman, A. M., Ten Bokkel Huinink, D., Fossion, L., Geenen, M. M., Hendriks, M. P., van de Luijtgaarden, A. C. M., Polee, M. B., Weijl, N. I., van de Wouw, A. J., de Wit, R., ... Gerritsen, W. R. (2021). Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry. European Urology Oncology, 4(4), 618-627. https://doi.org/10.1016/j.euo.2019.09.005

Kuppen, Malou C P ; Westgeest, Hans M ; van den Eertwegh, Alphonsus J M et al. / Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer : Results from the Dutch Castration-resistant Prostate Cancer Registry. In: European Urology Oncology. 2021 ; Vol. 4, No. 4. pp. 618-627.

@article{35bd558d0ff84612ac31e8c64d83badd,

title = "Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry",

abstract = "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.",

keywords = "Abiraterone acetate, Androgen-receptor targeting agents, Castration-resistant prostate cancer, Cross resistance, Enzalutamide, Real-world outcomes, Sequencing",

author = "Kuppen, \{Malou C P\} and Westgeest, \{Hans M\} and \{van den Eertwegh\}, \{Alphonsus J M\} and \{van Moorselaar\}, \{Reindert J A\} and \{van Oort\}, \{Inge M\} and Coenen, \{Juleon L L M\} and \{van den Bergh\}, \{A C M Fons\} and Niven Mehra and Somford, \{Diederik M\} and Bergman, \{Andre M\} and \{Ten Bokkel Huinink\}, Daan and Laurent Fossion and Geenen, \{Maud M\} and Hendriks, \{Mathijs P\} and \{van de Luijtgaarden\}, \{Addy C M\} and Polee, \{Marco B\} and Weijl, \{Nir I\} and \{van de Wouw\}, \{Agnes J\} and \{de Wit\}, Ronald and \{Uyl-de Groot\}, \{Carin A\} and Gerritsen, \{Winald R\}",

year = "2021",

month = aug,

day = "1",

doi = "10.1016/j.euo.2019.09.005",

language = "English",

volume = "4",

pages = "618--627",

journal = "European Urology Oncology",

issn = "2588-9311",

publisher = "Elsevier BV",

number = "4",

}

Kuppen, MCP, Westgeest, HM, van den Eertwegh, AJM, van Moorselaar, RJA, van Oort, IM, Coenen, JLLM, van den Bergh, ACMF, Mehra, N, Somford, DM, Bergman, AM, Ten Bokkel Huinink, D, Fossion, L, Geenen, MM, Hendriks, MP, van de Luijtgaarden, ACM, Polee, MB, Weijl, NI, van de Wouw, AJ, de Wit, R, Uyl-de Groot, CA & Gerritsen, WR 2021, 'Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry', European Urology Oncology, vol. 4, no. 4, pp. 618-627. https://doi.org/10.1016/j.euo.2019.09.005

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry. / Kuppen, Malou C P; Westgeest, Hans M; van den Eertwegh, Alphonsus J M et al.
In: European Urology Oncology, Vol. 4, No. 4, 01.08.2021, p. 618-627.

Research output: Contribution to journal › Article › Academic › peer-review

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

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 - https://www.scopus.com/pages/publications/85114120021

U2 - 10.1016/j.euo.2019.09.005

DO - 10.1016/j.euo.2019.09.005

M3 - Article

SN - 2588-9311

VL - 4

SP - 618

EP - 627

JO - European Urology Oncology

JF - European Urology Oncology

IS - 4

ER -

Kuppen MCP, Westgeest HM, van den Eertwegh AJM, van Moorselaar RJA, van Oort IM, Coenen JLLM et al. Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry. European Urology Oncology. 2021 Aug 1;4(4):618-627. Epub 2019 Oct 7. doi: 10.1016/j.euo.2019.09.005

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry

Abstract

UN SDGs

Keywords

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