The University of Southampton
University of Southampton Institutional Repository

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
f89e90e4-a419-41eb-9092-ddff5ba67cb2
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Mark, Michael
0751da15-1e84-42db-a045-eaec33e9ede0
Winterhalder, Ralph
786990a1-1278-4a7c-a63a-dd30c43e0505
Rothermundt, Christian
12e6bdd4-9859-4cef-b2b6-f1fbf5c21122
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
von Burg, Philippe
659891a2-359f-4427-966a-43f73a317096
Kenner, Heike
d136781b-b526-4c5e-8c50-b5b87d6e2a8d
Hayoz, Stefanie
d0d14ae3-e955-4e4f-b945-77dac6f74f92
Vilei, Simona Berardi
7fd5c314-95c5-44ad-a5d8-55968f0283a1
Rauch, Daniel
aac0c207-4afa-4e5a-849e-e38a011a57d7
Roggero, Enrico
eb78a47e-a7a1-4466-b507-e3f668374579
Mohaupt, Markus G.
5f8a1c65-04cd-4333-8167-00c3c5340b03
Bernhard, Jürg
fa97c3e1-8e29-4543-a321-ef5a09c992f4
Manetsch, Gabriela
49f7984f-ddd1-47b8-8d80-7d43c26e2666
Gillessen, Silke
2bc90f29-5ad5-45c7-88ae-19d4e9742531
Cathomas, Richard
f89e90e4-a419-41eb-9092-ddff5ba67cb2
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Mark, Michael
0751da15-1e84-42db-a045-eaec33e9ede0
Winterhalder, Ralph
786990a1-1278-4a7c-a63a-dd30c43e0505
Rothermundt, Christian
12e6bdd4-9859-4cef-b2b6-f1fbf5c21122
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
von Burg, Philippe
659891a2-359f-4427-966a-43f73a317096
Kenner, Heike
d136781b-b526-4c5e-8c50-b5b87d6e2a8d
Hayoz, Stefanie
d0d14ae3-e955-4e4f-b945-77dac6f74f92
Vilei, Simona Berardi
7fd5c314-95c5-44ad-a5d8-55968f0283a1
Rauch, Daniel
aac0c207-4afa-4e5a-849e-e38a011a57d7
Roggero, Enrico
eb78a47e-a7a1-4466-b507-e3f668374579
Mohaupt, Markus G.
5f8a1c65-04cd-4333-8167-00c3c5340b03
Bernhard, Jürg
fa97c3e1-8e29-4543-a321-ef5a09c992f4
Manetsch, Gabriela
49f7984f-ddd1-47b8-8d80-7d43c26e2666
Gillessen, Silke
2bc90f29-5ad5-45c7-88ae-19d4e9742531

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
__soton.ac.uk_ude_personalfiles_users_sjc7_mydesktop_SAKK 08-11 Manuscipt The Prostate.pdf - Accepted Manuscript
Download (839kB)

More information

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: http://eprints.soton.ac.uk/id/eprint/399182
ISSN: 0270-4137
PURE UUID: 8203c328-bef8-4f0d-af06-691e5931b81c
ORCID for Simon J. Crabb: ORCID iD orcid.org/0000-0003-3521-9064

Catalogue record

Date deposited: 08 Aug 2016 14:20
Last modified: 15 Mar 2024 05:47

Export record

Altmetrics

Contributors

Author: Richard Cathomas
Author: Simon J. Crabb ORCID iD
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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×