TY - JOUR
T1 - Age-stratified clinical outcomes and adverse events in patients with metastatic castration-sensitive prostate cancer receiving triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel
AU - Uchimoto, Taizo
AU - Hirosuna, Kensuke
AU - Niigawa, Heima
AU - Jo, Taisuke
AU - Morinaka, Hirofumi
AU - Fukuokaya, Wataru
AU - Yoshizawa, Atsuhiko
AU - Saruta, Masanobu
AU - Morita, Tsuyoshi
AU - Fujimoto, Saizo
AU - Yamamoto, Yutaka
AU - Sakamoto, Moritoshi
AU - Nishimura, Kazuki
AU - Maenosono, Ryoichi
AU - Tsujino, Takuya
AU - Nishio, Kyosuke
AU - Yoshikawa, Yuki
AU - Ichihashi, Atsushi
AU - Urabe, Fumihiko
AU - Mori, Keiichiro
AU - Yanagisawa, Takafumi
AU - Tsuzuki, Shunsuke
AU - Takahara, Kiyoshi
AU - Inamoto, Teruo
AU - Fujita, Kazutoshi
AU - Azuma, Haruhito
AU - Kimura, Takahiro
AU - Komura, Kazumasa
N1 - Publisher Copyright:
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PY - 2026/5
Y1 - 2026/5
N2 - Background: Triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel (DOC) has emerged as an intensified treatment option for metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated real-world prostate specific antigen (PSA) responses and adverse events (AEs) associated with triplet therapy, with a focus on age-specific differences. Methods: We performed a retrospective cohort study across six academic institutions in Japan between February 2023 and February 2025. A total of 137 patients with mCSPC who received triplet therapy were analyzed. PSA responses and AEs were assessed, including subgroup analyses by age (<75 vs ≥75 years). Results: The median age was 71 years, and 40 patients (29.2%) were aged ≥75 years. Six cycles of DOC were completed at similar rates in patients aged <75 years (66.0%) and ≥ 75 years (57.5%) (P = .435). The median baseline PSA was 298 ng/ml, and 107 patients (78.1%) met the CHAARTED high-volume criteria. At three months, the median [interquartile range] PSA decline was 99.8% [99.0–99.9]; 113 patients (92.6%) achieved a PSA decline >90%, and 35 patients (28.7%) achieved a PSA <0.2 ng/ml. During follow-up, the proportion achieving a PSA nadir <0.2 ng/ml did not differ significantly between patients aged <75 years (63.9%) and ≥ 75 years (55.0%) (P = .341). Grade ≥ 3 AEs occurred in 56 patients (40.9%), including febrile neutropenia in 29 patients (21.2%). The incidence of AEs did not differ significantly by age. Conclusions: In this real-world cohort, triplet therapy showed substantial PSA declines and acceptable tolerability, with no significant differences in short-term efficacy or safety between patients aged <75 and ≥ 75 years. These findings suggest that chronological age alone should not preclude consideration of triplet therapy in appropriately selected patients.
AB - Background: Triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel (DOC) has emerged as an intensified treatment option for metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated real-world prostate specific antigen (PSA) responses and adverse events (AEs) associated with triplet therapy, with a focus on age-specific differences. Methods: We performed a retrospective cohort study across six academic institutions in Japan between February 2023 and February 2025. A total of 137 patients with mCSPC who received triplet therapy were analyzed. PSA responses and AEs were assessed, including subgroup analyses by age (<75 vs ≥75 years). Results: The median age was 71 years, and 40 patients (29.2%) were aged ≥75 years. Six cycles of DOC were completed at similar rates in patients aged <75 years (66.0%) and ≥ 75 years (57.5%) (P = .435). The median baseline PSA was 298 ng/ml, and 107 patients (78.1%) met the CHAARTED high-volume criteria. At three months, the median [interquartile range] PSA decline was 99.8% [99.0–99.9]; 113 patients (92.6%) achieved a PSA decline >90%, and 35 patients (28.7%) achieved a PSA <0.2 ng/ml. During follow-up, the proportion achieving a PSA nadir <0.2 ng/ml did not differ significantly between patients aged <75 years (63.9%) and ≥ 75 years (55.0%) (P = .341). Grade ≥ 3 AEs occurred in 56 patients (40.9%), including febrile neutropenia in 29 patients (21.2%). The incidence of AEs did not differ significantly by age. Conclusions: In this real-world cohort, triplet therapy showed substantial PSA declines and acceptable tolerability, with no significant differences in short-term efficacy or safety between patients aged <75 and ≥ 75 years. These findings suggest that chronological age alone should not preclude consideration of triplet therapy in appropriately selected patients.
KW - PSA response
KW - adverse events
KW - darolutamide
KW - febrile neutropenia
KW - metastatic castration-sensitive prostate cancer
KW - triplet therapy
UR - https://www.scopus.com/pages/publications/105038232132
UR - https://www.scopus.com/pages/publications/105038232132#tab=citedBy
U2 - 10.1093/jjco/hyag011
DO - 10.1093/jjco/hyag011
M3 - Article
C2 - 41632522
AN - SCOPUS:105038232132
SN - 0368-2811
VL - 56
SP - 628
EP - 635
JO - Japanese journal of clinical oncology
JF - Japanese journal of clinical oncology
IS - 5
ER -
SDG 3 Good Health and Well-being