Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial.
Journal
JNCI cancer spectrum
ISSN: 2515-5091
Titre abrégé: JNCI Cancer Spectr
Pays: England
ID NLM: 101721827
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
26
10
2021
revised:
02
12
2021
accepted:
24
02
2022
pubmed:
26
7
2022
medline:
3
8
2022
entrez:
25
7
2022
Statut:
ppublish
Résumé
STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.
Sections du résumé
BACKGROUND
STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival.
METHODS
Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression).
RESULTS
Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity.
CONCLUSIONS
There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.
Identifiants
pubmed: 35877084
pii: 6649740
doi: 10.1093/jncics/pkac043
pmc: PMC9338456
pii:
doi:
Substances chimiques
Androgen Antagonists
0
Androgens
0
Docetaxel
15H5577CQD
Prostate-Specific Antigen
EC 3.4.21.77
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : CRUK_A12459
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_MC_UU_12023/25
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/25
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12518
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 3804
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00004/01
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press.
Références
J Clin Oncol. 2018 Apr 10;36(11):1080-1087
pubmed: 29384722
Eur Urol. 2015 Jun;67(6):1028-1038
pubmed: 25301760
Lancet. 2011 Dec 17;378(9809):2104-11
pubmed: 22056152
JAMA Oncol. 2019 May 01;5(5):623-632
pubmed: 30703190
Stat Med. 2011 Aug 30;30(19):2409-21
pubmed: 21611958
Lancet. 2022 Jan 29;399(10323):447-460
pubmed: 34953525
J Clin Oncol. 2022 Mar 10;40(8):825-836
pubmed: 34757812
N Engl J Med. 2015 Aug 20;373(8):737-46
pubmed: 26244877
Lancet. 2016 Mar 19;387(10024):1163-77
pubmed: 26719232
JAMA Oncol. 2016 Mar;2(3):348-57
pubmed: 26606329
J Clin Oncol. 2018 Apr 10;36(11):1088-1095
pubmed: 29522362
Eur Urol. 2016 Aug;70(2):256-62
pubmed: 26610858
BJU Int. 2009 Feb;103(4):464-9
pubmed: 18990168
Eur Urol Oncol. 2018 Dec;1(6):449-458
pubmed: 31158087
Lancet. 2009 Jan 24;373(9660):301-8
pubmed: 19091394
Lancet Oncol. 2015 Jul;16(7):787-94
pubmed: 26028518
Ann Oncol. 2019 Dec 1;30(12):1992-2003
pubmed: 31560068
BJU Int. 2011 Dec;108(11):1825-32
pubmed: 21615854
J Clin Oncol. 2017 Sep 20;35(27):3097-3104
pubmed: 28796587
Stat Med. 2002 Aug 15;21(15):2175-97
pubmed: 12210632
J Clin Oncol. 2018 May 20;36(15):1521-1539
pubmed: 29608397
Lancet Oncol. 2016 Feb;17(2):243-256
pubmed: 26718929
Ann Oncol. 2015 Sep;26 Suppl 5:v69-77
pubmed: 26205393
Lancet Oncol. 2013 Feb;14(2):149-58
pubmed: 23306100
BMJ Open. 2019 Sep 30;9(9):e030215
pubmed: 31575572