Cargando…

Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer

BACKGROUND: Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is li...

Descripción completa

Detalles Bibliográficos
Autores principales: Briones, Juan, Khan, Maira, Sidhu, Amanjot K., Zhang, Liying, Smoragiewicz, Martin, Emmenegger, Urban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138065/
https://www.ncbi.nlm.nih.gov/pubmed/34026638
http://dx.doi.org/10.3389/fonc.2021.658331
_version_ 1783695735691149312
author Briones, Juan
Khan, Maira
Sidhu, Amanjot K.
Zhang, Liying
Smoragiewicz, Martin
Emmenegger, Urban
author_facet Briones, Juan
Khan, Maira
Sidhu, Amanjot K.
Zhang, Liying
Smoragiewicz, Martin
Emmenegger, Urban
author_sort Briones, Juan
collection PubMed
description BACKGROUND: Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT). METHODS: We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints. RESULTS: After a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively. CONCLUSIONS: In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.
format Online
Article
Text
id pubmed-8138065
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81380652021-05-22 Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer Briones, Juan Khan, Maira Sidhu, Amanjot K. Zhang, Liying Smoragiewicz, Martin Emmenegger, Urban Front Oncol Oncology BACKGROUND: Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT). METHODS: We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints. RESULTS: After a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively. CONCLUSIONS: In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC. Frontiers Media S.A. 2021-05-07 /pmc/articles/PMC8138065/ /pubmed/34026638 http://dx.doi.org/10.3389/fonc.2021.658331 Text en Copyright © 2021 Briones, Khan, Sidhu, Zhang, Smoragiewicz and Emmenegger https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Briones, Juan
Khan, Maira
Sidhu, Amanjot K.
Zhang, Liying
Smoragiewicz, Martin
Emmenegger, Urban
Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title_full Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title_fullStr Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title_full_unstemmed Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title_short Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
title_sort population-based study of docetaxel or abiraterone effectiveness and predictive markers of progression free survival in metastatic castration-sensitive prostate cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138065/
https://www.ncbi.nlm.nih.gov/pubmed/34026638
http://dx.doi.org/10.3389/fonc.2021.658331
work_keys_str_mv AT brionesjuan populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer
AT khanmaira populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer
AT sidhuamanjotk populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer
AT zhangliying populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer
AT smoragiewiczmartin populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer
AT emmeneggerurban populationbasedstudyofdocetaxelorabirateroneeffectivenessandpredictivemarkersofprogressionfreesurvivalinmetastaticcastrationsensitiveprostatecancer