TY - JOUR
T1 - Immune-related adverse events in urothelial cancer patients
T2 - Adjustment for immortal time bias
AU - Otsuka, Hikari
AU - Kita, Yuki
AU - Ito, Katsuhiro
AU - Sano, Takeshi
AU - Inokuchi, Junichi
AU - Tomida, Ryotaro
AU - Takahashi, Atsushi
AU - Matsumoto, Kazumasa
AU - Kurahashi, Ryoma
AU - Ozaki, Yu
AU - Uegaki, Masayuki
AU - Maruyama, Satoru
AU - Mukai, Shoichiro
AU - Tsutsumi, Masakazu
AU - Kawahara, Takashi
AU - Segawa, Takehiko
AU - Kitamura, Hiroshi
AU - Morita, Satoshi
AU - Kobayashi, Takashi
N1 - Publisher Copyright:
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2022/11
Y1 - 2022/11
N2 - To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC.
AB - To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC.
KW - immortal time bias
KW - immune-related adverse events
KW - pembrolizumab
KW - therapeutic efficacy
KW - urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85137334242&partnerID=8YFLogxK
U2 - 10.1111/cas.15539
DO - 10.1111/cas.15539
M3 - 学術論文
C2 - 35997546
AN - SCOPUS:85137334242
SN - 1347-9032
VL - 113
SP - 3912
EP - 3921
JO - Cancer Science
JF - Cancer Science
IS - 11
ER -