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Orteronel switch maintenance therapy in metastatic castration resistant prostate cancer after first-line docetaxel: a multicenter, randomized, double-blind, placebo-controlled trial (SAKK 08/11)

Orteronel switch maintenance therapy in metastatic castration resistant prostate cancer after first-line docetaxel: a multicenter, randomized, double-blind, placebo-controlled trial (SAKK 08/11)
Orteronel switch maintenance therapy in metastatic castration resistant prostate cancer after first-line docetaxel: a multicenter, randomized, double-blind, placebo-controlled trial (SAKK 08/11)
BACKGROUND We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel.

METHODS Men with mCRPC and non-progressive disease after a cumulative dose of ?300mg/m2 docetaxel for first line treatment were randomized 1:1 to receive orteronel 300mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%).

RESULTS Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P¼0.001; HR 0.32; 95%CI 0.15–0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P¼0.02; HR 0.42; 95%CI 0.20–0.91) in the orteronel and placebo arm, respectively. PSA decline ?50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis.

CONCLUSIONS Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research.
castration-resistant prostate cancer, orteronel, maintenance, docetax
0270-4137
1519-1527
Cathomas, Richard
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Crabb, Simon J.
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Mark, Michael
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Winterhalder, Ralph
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Rothermundt, Christian
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Elliott, Tony
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von Burg, Philippe
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Kenner, Heike
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Hayoz, Stefanie
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Vilei, Simona Berardi
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Rauch, Daniel
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Roggero, Enrico
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Mohaupt, Markus G.
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Bernhard, Jürg
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Manetsch, Gabriela
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Gillessen, Silke
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Cathomas, Richard
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Crabb, Simon J.
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Mark, Michael
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Winterhalder, Ralph
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Rothermundt, Christian
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Elliott, Tony
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von Burg, Philippe
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Kenner, Heike
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Hayoz, Stefanie
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Vilei, Simona Berardi
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Rauch, Daniel
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Roggero, Enrico
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Mohaupt, Markus G.
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Bernhard, Jürg
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Manetsch, Gabriela
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Gillessen, Silke
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Cathomas, Richard, Crabb, Simon J., Mark, Michael, Winterhalder, Ralph, Rothermundt, Christian, Elliott, Tony, von Burg, Philippe, Kenner, Heike, Hayoz, Stefanie, Vilei, Simona Berardi, Rauch, Daniel, Roggero, Enrico, Mohaupt, Markus G., Bernhard, Jürg, Manetsch, Gabriela and Gillessen, Silke (2016) Orteronel switch maintenance therapy in metastatic castration resistant prostate cancer after first-line docetaxel: a multicenter, randomized, double-blind, placebo-controlled trial (SAKK 08/11). The Prostate, 76 (16), 1519-1527. (doi:10.1002/pros.23236). (PMID:27457964)

Record type: Article

Abstract

BACKGROUND We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel.

METHODS Men with mCRPC and non-progressive disease after a cumulative dose of ?300mg/m2 docetaxel for first line treatment were randomized 1:1 to receive orteronel 300mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%).

RESULTS Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P¼0.001; HR 0.32; 95%CI 0.15–0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P¼0.02; HR 0.42; 95%CI 0.20–0.91) in the orteronel and placebo arm, respectively. PSA decline ?50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis.

CONCLUSIONS Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research.

Text
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Accepted/In Press date: 12 July 2016
e-pub ahead of print date: 25 July 2016
Published date: 1 December 2016
Keywords: castration-resistant prostate cancer, orteronel, maintenance, docetax
Organisations: Cancer Sciences, Clinical Trials Unit

Identifiers

Local EPrints ID: 399182
URI: https://eprints.soton.ac.uk/id/eprint/399182
ISSN: 0270-4137
PURE UUID: 8203c328-bef8-4f0d-af06-691e5931b81c

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Date deposited: 08 Aug 2016 14:20
Last modified: 21 Feb 2018 05:02

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Contributors

Author: Richard Cathomas
Author: Simon J. Crabb
Author: Michael Mark
Author: Ralph Winterhalder
Author: Christian Rothermundt
Author: Tony Elliott
Author: Philippe von Burg
Author: Heike Kenner
Author: Stefanie Hayoz
Author: Simona Berardi Vilei
Author: Daniel Rauch
Author: Enrico Roggero
Author: Markus G. Mohaupt
Author: Jürg Bernhard
Author: Gabriela Manetsch
Author: Silke Gillessen

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