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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

Merseburger, Axel S. ; Agarwal, Neeraj ; Bhaumik, Amitabha ; Lefresne, Florence ; Karsh, Laurence I. ; Pereira de Santana Gomes, Andrea J. ; Soto, Álvaro Juárez ; Given, Robert W. ; Brookman-May, Sabine D. and Mundle, Suneel D. , et al. (2023) In European Journal of Cancer 193.
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 = 0.68 [95% confidence interval: 0.53–0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40–1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33–1.44]; p = 0.32) and metachronous/low-volume (0.22 [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. Clinical Trial Registration: NCT02489318.

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publication status
published
subject
keywords
High-volume, Low-volume, mCSPC, Metachronous, Oligometastatic, Polymetastatic, Synchronous
in
European Journal of Cancer
volume
193
article number
113290
publisher
Elsevier
external identifiers
  • scopus:85171787422
  • pmid:37708629
ISSN
0959-8049
DOI
10.1016/j.ejca.2023.113290
language
English
LU publication?
yes
id
fd608b4b-8ffc-4b11-8564-ccad6210e5e3
date added to LUP
2023-12-07 10:33:23
date last changed
2024-11-17 02:52:55
@article{fd608b4b-8ffc-4b11-8564-ccad6210e5e3,
  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 = 0.68 [95% confidence interval: 0.53–0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40–1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33–1.44]; p = 0.32) and metachronous/low-volume (0.22 [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. Clinical Trial Registration: NCT02489318.</p>}},
  author       = {{Merseburger, Axel S. and Agarwal, Neeraj and Bhaumik, Amitabha and Lefresne, Florence and Karsh, Laurence I. and Pereira de Santana Gomes, Andrea J. and Soto, Álvaro Juárez and Given, Robert W. and Brookman-May, Sabine D. and Mundle, Suneel D. and McCarthy, Sharon A. and Uemura, Hirotsugu and Chowdhury, Simon and Chi, Kim N. and Bjartell, Anders}},
  issn         = {{0959-8049}},
  keywords     = {{High-volume; Low-volume; mCSPC; Metachronous; Oligometastatic; Polymetastatic; Synchronous}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{European Journal of Cancer}},
  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}},
  url          = {{http://dx.doi.org/10.1016/j.ejca.2023.113290}},
  doi          = {{10.1016/j.ejca.2023.113290}},
  volume       = {{193}},
  year         = {{2023}},
}