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Апалутамид в комбинации с андрогендепривационной терапией в клинических подгруппах пациентов с метастатическим кастрационно-чувствительным раком предстательной железы : подгрупповой анализ рандомизированного клинического исследования TITAN

Merseburger, A. S. ; Agarwal, N. ; Bhaumik, A. ; Lefresne, F. ; Karsh, L. I. ; de Santana Gomes, A. J.Pereira ; Soto, Juárez ; Given, R. W. ; Brookman-May, S. D. and Mundle, S. D. , et al. (2024) In Onkourologiya 20(1). p.79-93
Abstract

Background. Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. Methods. These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial... (More)

Background. Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. Methods. These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. Results. Of 1052 patients, 63 %, 81 %, 54 %, 27 %, 5.7 %, and 8.0 % had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio (HR) 0.68; 95 % confidence interval (CI) 0.53–0.87; p = 0.002), synchronous/low-volume (HR 0.65; 95 % CI 0.40–1.05; p = 0.08), metachronous/high-volume (HR 0.69; 95 % CI 0.33–1.44; p = 0.32) and metachronous/low-volume (HR 0.22; 95 % CI 0.09–0.55; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. Conclusion. TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.

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alternative title
Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer : a subgroup analysis of the randomised clinical TITAN study
publishing date
type
Contribution to journal
publication status
published
subject
keywords
high-volume, low-volume, metachronous, metastatic castration-sensitive prostate cancer, oligometastatic, polymetastatic, synchronous
in
Onkourologiya
volume
20
issue
1
pages
15 pages
publisher
ABV-press Publishing House
external identifiers
  • scopus:85195809981
ISSN
1726-9776
DOI
10.17650/1726-9776-2024-20-1-79-93
language
Russian
LU publication?
yes
id
108e49ac-61d6-49c9-922a-b9cc29334138
date added to LUP
2024-09-09 10:50:33
date last changed
2024-09-09 10:51:03
@article{108e49ac-61d6-49c9-922a-b9cc29334138,
  abstract     = {{<p>Background. Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. Methods. These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (&gt;5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. Results. Of 1052 patients, 63 %, 81 %, 54 %, 27 %, 5.7 %, and 8.0 % had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio (HR) 0.68; 95 % confidence interval (CI) 0.53–0.87; p = 0.002), synchronous/low-volume (HR 0.65; 95 % CI 0.40–1.05; p = 0.08), metachronous/high-volume (HR 0.69; 95 % CI 0.33–1.44; p = 0.32) and metachronous/low-volume (HR 0.22; 95 % CI 0.09–0.55; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. Conclusion. TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.</p>}},
  author       = {{Merseburger, A. S. and Agarwal, N. and Bhaumik, A. and Lefresne, F. and Karsh, L. I. and de Santana Gomes, A. J.Pereira and Soto, Juárez and Given, R. W. and Brookman-May, S. D. and Mundle, S. D. and McCarthy, S. A. and Uemura, H. and Chowdhury, S. and Chi, K. N. and Bjartell, A.}},
  issn         = {{1726-9776}},
  keywords     = {{high-volume; low-volume; metachronous; metastatic castration-sensitive prostate cancer; oligometastatic; polymetastatic; synchronous}},
  language     = {{rus}},
  number       = {{1}},
  pages        = {{79--93}},
  publisher    = {{ABV-press Publishing House}},
  series       = {{Onkourologiya}},
  title        = {{Апалутамид в комбинации с андрогендепривационной терапией в клинических подгруппах пациентов с метастатическим кастрационно-чувствительным раком предстательной железы : подгрупповой анализ рандомизированного клинического исследования TITAN}},
  url          = {{http://dx.doi.org/10.17650/1726-9776-2024-20-1-79-93}},
  doi          = {{10.17650/1726-9776-2024-20-1-79-93}},
  volume       = {{20}},
  year         = {{2024}},
}