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Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer

Chowdhury, S. ; Bjartell, A. LU ; Agarwal, N. ; Chung, B. H. ; Given, R. W. ; Pereira de Santana Gomes, A. J. ; Merseburger, A. S. ; Özgüroğlu, M. ; Juárez Soto, Soto and Uemura, H. , et al. (2023) In Annals of Oncology 34(5). p.477-485
Abstract

Background: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. Patients and methods: Patients received apalutamide (240 mg/day) or placebo plus ADT (1: 1). This post hoc exploratory analysis... (More)

Background: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. Patients and methods: Patients received apalutamide (240 mg/day) or placebo plus ADT (1: 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months’ follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months’ follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan–Meier method, and Cox proportional hazards model. Results: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. Conclusions: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
castration resistance, mCSPC, overall survival, PSA progression, radiographic progression-free survival
in
Annals of Oncology
volume
34
issue
5
pages
9 pages
publisher
Oxford University Press
external identifiers
  • pmid:36858151
  • scopus:85151883498
ISSN
0923-7534
DOI
10.1016/j.annonc.2023.02.009
language
English
LU publication?
yes
id
d137edd3-48d0-4461-bba0-993b79d70dd7
date added to LUP
2023-06-12 14:59:47
date last changed
2024-04-19 23:50:03
@article{d137edd3-48d0-4461-bba0-993b79d70dd7,
  abstract     = {{<p>Background: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. Patients and methods: Patients received apalutamide (240 mg/day) or placebo plus ADT (1: 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months’ follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months’ follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan–Meier method, and Cox proportional hazards model. Results: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P &lt; 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. Conclusions: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.</p>}},
  author       = {{Chowdhury, S. and Bjartell, A. and Agarwal, N. and Chung, B. H. and Given, R. W. and Pereira de Santana Gomes, A. J. and Merseburger, A. S. and Özgüroğlu, M. and Juárez Soto, Soto and Uemura, H. and Ye, D. and Brookman-May, S. D. and Londhe, A. and Bhaumik, A. and Mundle, S. D. and Larsen, J. S. and McCarthy, S. A. and Chi, K. N.}},
  issn         = {{0923-7534}},
  keywords     = {{castration resistance; mCSPC; overall survival; PSA progression; radiographic progression-free survival}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{477--485}},
  publisher    = {{Oxford University Press}},
  series       = {{Annals of Oncology}},
  title        = {{Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer}},
  url          = {{http://dx.doi.org/10.1016/j.annonc.2023.02.009}},
  doi          = {{10.1016/j.annonc.2023.02.009}},
  volume       = {{34}},
  year         = {{2023}},
}