Treatment of Metastasized Prostate Cancer Beyond Progression After Upfront Docetaxel-A Real-world Data Assessment.


Journal

European urology focus
ISSN: 2405-4569
Titre abrégé: Eur Urol Focus
Pays: Netherlands
ID NLM: 101665661

Informations de publication

Date de publication:
Nov 2021
Historique:
received: 27 05 2020
revised: 15 06 2020
accepted: 25 06 2020
pubmed: 13 7 2020
medline: 14 4 2022
entrez: 13 7 2020
Statut: ppublish

Résumé

Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited.

Sections du résumé

BACKGROUND BACKGROUND
Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce.
OBJECTIVE OBJECTIVE
To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting.
DESIGN, SETTING, AND PARTICIPANTS METHODS
This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS METHODS
Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model.
RESULTS AND LIMITATIONS CONCLUSIONS
Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature.
CONCLUSIONS CONCLUSIONS
In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer.
PATIENT SUMMARY RESULTS
We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited.

Identifiants

pubmed: 32653263
pii: S2405-4569(20)30184-X
doi: 10.1016/j.euf.2020.06.018
pii:
doi:

Substances chimiques

Androgen Antagonists 0
Androgens 0
Docetaxel 15H5577CQD

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1308-1315

Informations de copyright

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Igor Tsaur (I)

Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany. Electronic address: igor.tsaur@unimedizin-mainz.de.

Isabel Heidegger (I)

Department of Urology, Medical University Innsbruck, Innsbruck, Austria.

Roderick C N van den Bergh (RCN)

Department of Urology, St Antonius Hospital, Utrecht, The Netherlands.

Jasmin Bektic (J)

Department of Urology, Medical University Innsbruck, Innsbruck, Austria.

Hendrik Borgmann (H)

Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany.

Silvia Foti (S)

Division of Oncology/Unit of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Jarmo C B Hunting (JCB)

Department of Clinical Oncology, St Antonius Hospital, Utrecht, The Netherlands.

Alexander Kretschmer (A)

Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany.

Guillaume Ploussard (G)

Department of Urology, La Croix du Sud Hospital, Toulouse, France; Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.

Derya Tilki (D)

Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital-Hamburg Eppendorf, Hamburg, Germany.

Giorgio Gandaglia (G)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Robert Dotzauer (R)

Department of Urology and Pediatric Urology, University Medicine Mainz, Mainz, Germany.

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Classifications MeSH