Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer.
apalutamide
non-metastatic castration-resistant prostate cancer
overall survival
subsequent therapy
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
pubmed:
29
9
2019
medline:
4
8
2020
entrez:
28
9
2019
Statut:
ppublish
Résumé
In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2). One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed. Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed. In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.
Sections du résumé
BACKGROUND
In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).
METHODS
One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed.
RESULTS
Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed.
CONCLUSION
In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.
Identifiants
pubmed: 31560066
pii: S0923-7534(20)32601-6
doi: 10.1093/annonc/mdz397
pmc: PMC6927320
pii:
doi:
Substances chimiques
Androgen Receptor Antagonists
0
Placebos
0
Thiohydantoins
0
apalutamide
0
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1813-1820Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Références
Cancer Res. 2012 Mar 15;72(6):1494-503
pubmed: 22266222
Eur Urol. 2019 Feb;75(2):285-293
pubmed: 30119985
Cancer. 2011 May 15;117(10):2077-85
pubmed: 21523719
Oncogene. 2013 Dec 5;32(49):5501-11
pubmed: 23752182
Cold Spring Harb Perspect Med. 2017 Sep 1;7(9):
pubmed: 28389515
Lancet. 2018 Dec 1;392(10162):2353-2366
pubmed: 30355464
Eur Urol. 2019 Jan;75(1):44-60
pubmed: 30286948
N Engl J Med. 2018 Apr 12;378(15):1408-1418
pubmed: 29420164
Endocr Relat Cancer. 2010 Oct 29;17(4):R305-15
pubmed: 20861285
J Clin Oncol. 2005 May 1;23(13):2918-25
pubmed: 15860850
J Clin Oncol. 2013 Oct 20;31(30):3800-6
pubmed: 24043751