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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

Abstract

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.

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.

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.

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.

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.

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.

More about this publication

European urology oncology

Volume 4
Issue nr. 4
Pages 618-627
Publication date 01-08-2021

Full text links

Publisher website (DOI) 10.1016/j.euo.2019.09.005
Europe PubMed Central 31601523
Pubmed 31601523

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