Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction.

Abstract

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.

• Authors: Yuki Kita, Katsuhiro Ito, Sohei Kanda, Akira Joraku, Ritsuki Yamaguchi, Yosuke Shimizu, Naoki Hayata, Shinya Somiya, Noboru Shibasaki, Takahiro Kimura, Kensuke Hikami, Takeshi Yamada, Takashige Abe, Kazunari Tsuchihashi, Shuichi Tatarano, Hiroyuki Nishiyama, Hiroshi Kitamura, Takashi Kobayashi
• Journal: Urologic oncology (Urol Oncol) Vol. 40 Issue 9 Pg. 410.e11-410.e18 (09 2022) ISSN: 1873-2496 [Electronic] United States
• PMID: 35551861 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• pembrolizumab

Topics

• Antibodies, Monoclonal, Humanized
• Carcinoma, Transitional Cell
• Humans
• Kidney Diseases
• Treatment Outcome
• Urinary Bladder Neoplasms