PMID- 35551861
OWN - NLM
STAT- MEDLINE
DCOM- 20220830
LR  - 20220922
IS  - 1873-2496 (Electronic)
IS  - 1078-1439 (Linking)
VI  - 40
IP  - 9
DP  - 2022 Sep
TI  - Tolerability and treatment outcome of pembrolizumab in patients with advanced 
      urothelial carcinoma and severe renal dysfunction.
PG  - 410.e11-410.e18
LID - S1078-1439(22)00115-6 [pii]
LID - 10.1016/j.urolonc.2022.04.005 [doi]
AB  - OBJECTIVES: Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the 
      treatment of advanced urothelial carcinoma. However, the tolerability and 
      outcomes of pembrolizumab in patients with severe renal dysfunction [creatinine 
      clearance (CrCl) <30 ml/min] are unclear because no clinical trials included such 
      patients. We analyzed the safety profile and outcomes of these patients in the 
      real world. METHODS: We extracted data for 739 pembrolizumab-treated patients 
      from a Japanese nationwide cohort of platinum-refractory metastatic urothelial 
      carcinoma. Using propensity score matching, the overall survival (OS) and adverse 
      events (AEs) of patients with CrCl <30 and >/=30 were compared. RESULTS: Ninety-two 
      patients (12.4%) had CrCl <30 ml/min. The median number of doses was similar 
      between the CrCl >/= 30 and CrCl <30 groups (5 and 4, respectively), and there was 
      no difference in the frequency of grade >/=2 treatment-related AEs between the 
      groups (35.5% vs. 35.7%). The overall response rate was similar between the 
      groups (27.2% vs. 29.7%, P = 0.184). Using propensity score matching, the median 
      OS times in the CrCl >/=30 and CrCl <30 groups were 10.3 (95% confidence interval 
      [CI] = CI 7.3-13.0) and 8.1 months (95% CI = 5.4-14.6, P = 0.626), respectively. 
      The 1-year OS rates in these groups were 41.5% and 38.2%, respectively, and the 
      2-year OS rates were 21.3% and 20.2%, respectively. In multivariate Cox 
      regression analysis, performance status >/=2 (hazard ratio [HR] = 5.56, 95% 
      CI = 2.64-11.71, P < 0.0001) and neutrophil-to-lymphocyte ratio >/=3 (HR = 2.20, 
      95% CI =1.15-4.19, P = 0.013) were independently associated with patient 
      prognosis in the CrCl <30 group. CONCLUSIONS: This report illustrated that 
      pembrolizumab can be safely administered to patients with severe renal 
      dysfunction, who had similar outcomes as patients without severe renal 
      dysfunction.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Kita, Yuki
AU  - Kita Y
AD  - Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Ito, Katsuhiro
AU  - Ito K
AD  - Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Kanda, Sohei
AU  - Kanda S
AD  - Department of Urology, Akita University, Akita, Japan.
FAU - Joraku, Akira
AU  - Joraku A
AD  - Department of Urology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
FAU - Yamaguchi, Ritsuki
AU  - Yamaguchi R
AD  - Department of Urology, Kobe City Nishi-Kobe Medical Center, Kobe, Japan.
FAU - Shimizu, Yosuke
AU  - Shimizu Y
AD  - Department of Urology, Kobe City Nishi-Kobe Medical Center, Kobe, Japan.
FAU - Hayata, Naoki
AU  - Hayata N
AD  - Department of Urology, Kyoto Medical Center, Kyoto, Japan.
FAU - Somiya, Shinya
AU  - Somiya S
AD  - Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan.
FAU - Shibasaki, Noboru
AU  - Shibasaki N
AD  - Department of Urology, Otsu City Hospital, Otsu, Japan.
FAU - Kimura, Takahiro
AU  - Kimura T
AD  - Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
FAU - Hikami, Kensuke
AU  - Hikami K
AD  - Department of Urology, Japanese Red Cross Wakayama Medical Center, Wakayama, 
      Japan.
FAU - Yamada, Takeshi
AU  - Yamada T
AD  - Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
FAU - Abe, Takashige
AU  - Abe T
AD  - Department of Urology, Hokkaido University Graduate School of Medcine, Sapporo, 
      Japan.
FAU - Tsuchihashi, Kazunari
AU  - Tsuchihashi K
AD  - Department of Urology, Japanese Red Cross Otsu Hospital, Otsu, Japan.
FAU - Tatarano, Shuichi
AU  - Tatarano S
AD  - Department of Urology, Kagoshima University, Kagoshima, Japan.
FAU - Nishiyama, Hiroyuki
AU  - Nishiyama H
AD  - Department of Urology, University of Tsukuba, Tsukuba, Japan.
FAU - Kitamura, Hiroshi
AU  - Kitamura H
AD  - Department of Urology, University of Toyama, Toyama, Japan.
FAU - Kobayashi, Takashi
AU  - Kobayashi T
AD  - Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. Electronic address: selecao@kuhp.kyoto-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20220509
PL  - United States
TA  - Urol Oncol
JT  - Urologic oncology
JID - 9805460
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized
MH  - *Carcinoma, Transitional Cell
MH  - Humans
MH  - *Kidney Diseases
MH  - Treatment Outcome
MH  - *Urinary Bladder Neoplasms
OTO - NOTNLM
OT  - Creatinine clearance
OT  - Immune checkpoint inhibitor
OT  - Pembrolizumab
OT  - Renal dysfunction
OT  - Urothelial carcinoma
EDAT- 2022/05/14 06:00
MHDA- 2022/08/31 06:00
CRDT- 2022/05/13 13:52
PHST- 2022/01/28 00:00 [received]
PHST- 2022/04/04 00:00 [revised]
PHST- 2022/04/08 00:00 [accepted]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/08/31 06:00 [medline]
PHST- 2022/05/13 13:52 [entrez]
AID - S1078-1439(22)00115-6 [pii]
AID - 10.1016/j.urolonc.2022.04.005 [doi]
PST - ppublish
SO  - Urol Oncol. 2022 Sep;40(9):410.e11-410.e18. doi: 10.1016/j.urolonc.2022.04.005. 
      Epub 2022 May 9.