Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation

Sushil K Badrising, Vincent van der Noort, Alfons J M van den Eertwegh, Paul Hamberg, Inge M van Oort, Hendrik P van den Berg, Maartje Los, Maureen J B Aarts, Jules L L M Coenen, Hans Gelderblom, Igle J de Jong, Emile D Kerver, Suzan Vrijaldenhoven, Theo van Voorthuizen, Fabienne Warmerdam, John B Haanen, Andries M Bergman, Dutch Uro-Oncology Studygroup

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized.

METHODS: 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated.

RESULTS: Median Progression-Free Survival was 12.2 weeks (95%CI 11.7-14.3) and Overall Survival 43.5 weeks (95%CI 37.4-61.2). There were 26 (25%) Enz-responders and 76 (75%) non-responders. Significant higher percentages of Gleason scores ≥ 8 and PSA doubling times (PSA-DT) <3 months were found in Enz responders than in non-responders. The interval between end of AA and start of Enz treatment (IAE) for responders was 24.6 weeks (IQR 4.0-48.1) and 8.9 weeks for non-responders (IQR 3.7-25.9) (P = 0.08). In an IAE <40 days subgroup (34 patients), Enz responses were related to AA non-responsiveness, while univariate and logistic regression analysis of baseline criteria of a subgroup of patients with an IAE ≥ 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT <3 months, Gleason scores ≥ 8 and IAE's between Enz responders and non-responders.

CONCLUSIONS: PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT <3 months. Identification of these patients might be of value for sequencing of treatment options.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalProstate
Volume76
Issue number1
DOIs
Publication statusPublished - Jan 2016

Cite this

Badrising, Sushil K ; van der Noort, Vincent ; van den Eertwegh, Alfons J M ; Hamberg, Paul ; van Oort, Inge M ; van den Berg, Hendrik P ; Los, Maartje ; Aarts, Maureen J B ; Coenen, Jules L L M ; Gelderblom, Hans ; de Jong, Igle J ; Kerver, Emile D ; Vrijaldenhoven, Suzan ; van Voorthuizen, Theo ; Warmerdam, Fabienne ; Haanen, John B ; Bergman, Andries M ; Dutch Uro-Oncology Studygroup. / Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation. In: Prostate. 2016 ; Vol. 76, No. 1. pp. 32-40.
@article{a3a896753daa49599d9a2195d9e7475e,
title = "Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation",
abstract = "BACKGROUND: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1{\%} of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized.METHODS: 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated.RESULTS: Median Progression-Free Survival was 12.2 weeks (95{\%}CI 11.7-14.3) and Overall Survival 43.5 weeks (95{\%}CI 37.4-61.2). There were 26 (25{\%}) Enz-responders and 76 (75{\%}) non-responders. Significant higher percentages of Gleason scores ≥ 8 and PSA doubling times (PSA-DT) <3 months were found in Enz responders than in non-responders. The interval between end of AA and start of Enz treatment (IAE) for responders was 24.6 weeks (IQR 4.0-48.1) and 8.9 weeks for non-responders (IQR 3.7-25.9) (P = 0.08). In an IAE <40 days subgroup (34 patients), Enz responses were related to AA non-responsiveness, while univariate and logistic regression analysis of baseline criteria of a subgroup of patients with an IAE ≥ 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT <3 months, Gleason scores ≥ 8 and IAE's between Enz responders and non-responders.CONCLUSIONS: PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT <3 months. Identification of these patients might be of value for sequencing of treatment options.",
keywords = "Aged, Androstenes, Antineoplastic Agents, Disease-Free Survival, Drug Monitoring, Drug Resistance, Neoplasm, Drug Substitution, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Netherlands, Phenylthiohydantoin, Prognosis, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant, Retrospective Studies, Taxoids, Treatment Outcome, Journal Article",
author = "Badrising, {Sushil K} and {van der Noort}, Vincent and {van den Eertwegh}, {Alfons J M} and Paul Hamberg and {van Oort}, {Inge M} and {van den Berg}, {Hendrik P} and Maartje Los and Aarts, {Maureen J B} and Coenen, {Jules L L M} and Hans Gelderblom and {de Jong}, {Igle J} and Kerver, {Emile D} and Suzan Vrijaldenhoven and {van Voorthuizen}, Theo and Fabienne Warmerdam and Haanen, {John B} and Bergman, {Andries M} and {Dutch Uro-Oncology Studygroup}",
note = "{\circledC} 2015 Wiley Periodicals, Inc.",
year = "2016",
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doi = "10.1002/pros.23094",
language = "English",
volume = "76",
pages = "32--40",
journal = "Prostate",
issn = "0270-4137",
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Badrising, SK, van der Noort, V, van den Eertwegh, AJM, Hamberg, P, van Oort, IM, van den Berg, HP, Los, M, Aarts, MJB, Coenen, JLLM, Gelderblom, H, de Jong, IJ, Kerver, ED, Vrijaldenhoven, S, van Voorthuizen, T, Warmerdam, F, Haanen, JB, Bergman, AM & Dutch Uro-Oncology Studygroup 2016, 'Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation' Prostate, vol. 76, no. 1, pp. 32-40. https://doi.org/10.1002/pros.23094

Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation. / Badrising, Sushil K; van der Noort, Vincent; van den Eertwegh, Alfons J M; Hamberg, Paul; van Oort, Inge M; van den Berg, Hendrik P; Los, Maartje; Aarts, Maureen J B; Coenen, Jules L L M; Gelderblom, Hans; de Jong, Igle J; Kerver, Emile D; Vrijaldenhoven, Suzan; van Voorthuizen, Theo; Warmerdam, Fabienne; Haanen, John B; Bergman, Andries M; Dutch Uro-Oncology Studygroup.

In: Prostate, Vol. 76, No. 1, 01.2016, p. 32-40.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation

AU - Badrising, Sushil K

AU - van der Noort, Vincent

AU - van den Eertwegh, Alfons J M

AU - Hamberg, Paul

AU - van Oort, Inge M

AU - van den Berg, Hendrik P

AU - Los, Maartje

AU - Aarts, Maureen J B

AU - Coenen, Jules L L M

AU - Gelderblom, Hans

AU - de Jong, Igle J

AU - Kerver, Emile D

AU - Vrijaldenhoven, Suzan

AU - van Voorthuizen, Theo

AU - Warmerdam, Fabienne

AU - Haanen, John B

AU - Bergman, Andries M

AU - Dutch Uro-Oncology Studygroup

N1 - © 2015 Wiley Periodicals, Inc.

PY - 2016/1

Y1 - 2016/1

N2 - BACKGROUND: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized.METHODS: 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated.RESULTS: Median Progression-Free Survival was 12.2 weeks (95%CI 11.7-14.3) and Overall Survival 43.5 weeks (95%CI 37.4-61.2). There were 26 (25%) Enz-responders and 76 (75%) non-responders. Significant higher percentages of Gleason scores ≥ 8 and PSA doubling times (PSA-DT) <3 months were found in Enz responders than in non-responders. The interval between end of AA and start of Enz treatment (IAE) for responders was 24.6 weeks (IQR 4.0-48.1) and 8.9 weeks for non-responders (IQR 3.7-25.9) (P = 0.08). In an IAE <40 days subgroup (34 patients), Enz responses were related to AA non-responsiveness, while univariate and logistic regression analysis of baseline criteria of a subgroup of patients with an IAE ≥ 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT <3 months, Gleason scores ≥ 8 and IAE's between Enz responders and non-responders.CONCLUSIONS: PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT <3 months. Identification of these patients might be of value for sequencing of treatment options.

AB - BACKGROUND: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized.METHODS: 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated.RESULTS: Median Progression-Free Survival was 12.2 weeks (95%CI 11.7-14.3) and Overall Survival 43.5 weeks (95%CI 37.4-61.2). There were 26 (25%) Enz-responders and 76 (75%) non-responders. Significant higher percentages of Gleason scores ≥ 8 and PSA doubling times (PSA-DT) <3 months were found in Enz responders than in non-responders. The interval between end of AA and start of Enz treatment (IAE) for responders was 24.6 weeks (IQR 4.0-48.1) and 8.9 weeks for non-responders (IQR 3.7-25.9) (P = 0.08). In an IAE <40 days subgroup (34 patients), Enz responses were related to AA non-responsiveness, while univariate and logistic regression analysis of baseline criteria of a subgroup of patients with an IAE ≥ 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT <3 months, Gleason scores ≥ 8 and IAE's between Enz responders and non-responders.CONCLUSIONS: PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT <3 months. Identification of these patients might be of value for sequencing of treatment options.

KW - Aged

KW - Androstenes

KW - Antineoplastic Agents

KW - Disease-Free Survival

KW - Drug Monitoring

KW - Drug Resistance, Neoplasm

KW - Drug Substitution

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Staging

KW - Netherlands

KW - Phenylthiohydantoin

KW - Prognosis

KW - Prostate-Specific Antigen

KW - Prostatic Neoplasms, Castration-Resistant

KW - Retrospective Studies

KW - Taxoids

KW - Treatment Outcome

KW - Journal Article

U2 - 10.1002/pros.23094

DO - 10.1002/pros.23094

M3 - Article

VL - 76

SP - 32

EP - 40

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 1

ER -