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Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer

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). Overa...

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Autores principales: Small, E J, Saad, F, Chowdhury, S, Oudard, S, Hadaschik, B A, Graff, J N, Olmos, D, Mainwaring, P N, Lee, J Y, Uemura, H, De Porre, P, Smith, A A, Zhang, K, Lopez-Gitlitz, A, Smith, M R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/
https://www.ncbi.nlm.nih.gov/pubmed/31560066
http://dx.doi.org/10.1093/annonc/mdz397
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author Small, E J
Saad, F
Chowdhury, S
Oudard, S
Hadaschik, B A
Graff, J N
Olmos, D
Mainwaring, P N
Lee, J Y
Uemura, H
De Porre, P
Smith, A A
Zhang, K
Lopez-Gitlitz, A
Smith, M R
author_facet Small, E J
Saad, F
Chowdhury, S
Oudard, S
Hadaschik, B A
Graff, J N
Olmos, D
Mainwaring, P N
Lee, J Y
Uemura, H
De Porre, P
Smith, A A
Zhang, K
Lopez-Gitlitz, A
Smith, M R
author_sort Small, E J
collection PubMed
description 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.
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spelling pubmed-69273202019-12-27 Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer Small, E J Saad, F Chowdhury, S Oudard, S Hadaschik, B A Graff, J N Olmos, D Mainwaring, P N Lee, J Y Uemura, H De Porre, P Smith, A A Zhang, K Lopez-Gitlitz, A Smith, M R Ann Oncol Original Articles 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. Oxford University Press 2019-11 2019-09-27 /pmc/articles/PMC6927320/ /pubmed/31560066 http://dx.doi.org/10.1093/annonc/mdz397 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Small, E J
Saad, F
Chowdhury, S
Oudard, S
Hadaschik, B A
Graff, J N
Olmos, D
Mainwaring, P N
Lee, J Y
Uemura, H
De Porre, P
Smith, A A
Zhang, K
Lopez-Gitlitz, A
Smith, M R
Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title_full Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title_fullStr Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title_full_unstemmed Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title_short Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
title_sort apalutamide and overall survival in non-metastatic castration-resistant prostate cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/
https://www.ncbi.nlm.nih.gov/pubmed/31560066
http://dx.doi.org/10.1093/annonc/mdz397
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