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Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer : Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study

Chi, Kim N. ; Chowdhury, Simon ; Bjartell, Anders LU ; Chung, Byung Ha ; Pereira de Santana Gomes, Andrea J. ; Given, Robert ; Juárez, Alvaro ; Merseburger, Axel S. ; Özgüroğlu, Mustafa and Uemura, Hirotsugu , et al. (2021) In Journal of clinical oncology : official journal of the American Society of Clinical Oncology 39(20). p.2294-2303
Abstract

PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox... (More)

PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.

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Contribution to journal
publication status
published
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in
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
volume
39
issue
20
pages
10 pages
publisher
American Society of Clinical Oncology
external identifiers
  • pmid:33914595
  • scopus:85106883025
ISSN
0732-183X
DOI
10.1200/JCO.20.03488
language
English
LU publication?
yes
id
e4297468-cc47-46e4-aebe-78d0333a98ac
date added to LUP
2022-03-08 13:46:48
date last changed
2024-06-10 11:08:13
@article{e4297468-cc47-46e4-aebe-78d0333a98ac,
  abstract     = {{<p>PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P &lt; .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P &lt; .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P &lt; .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.</p>}},
  author       = {{Chi, Kim N. and Chowdhury, Simon and Bjartell, Anders and Chung, Byung Ha and Pereira de Santana Gomes, Andrea J. and Given, Robert and Juárez, Alvaro and Merseburger, Axel S. and Özgüroğlu, Mustafa and Uemura, Hirotsugu and Ye, Dingwei and Brookman-May, Sabine and Mundle, Suneel D. and McCarthy, Sharon A. and Larsen, Julie S. and Sun, Weili and Bevans, Katherine B. and Zhang, Ke and Bandyopadhyay, Nibedita and Agarwal, Neeraj}},
  issn         = {{0732-183X}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{20}},
  pages        = {{2294--2303}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of clinical oncology : official journal of the American Society of Clinical Oncology}},
  title        = {{Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer : Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study}},
  url          = {{http://dx.doi.org/10.1200/JCO.20.03488}},
  doi          = {{10.1200/JCO.20.03488}},
  volume       = {{39}},
  year         = {{2021}},
}