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Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis

BACKGROUND: Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retros...

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Autores principales: Kawai, Taketo, Taguchi, Satoru, Nakagawa, Tohru, Kamei, Jun, Nakamura, Yu, Obinata, Daisuke, Yamaguchi, Kenya, Kaneko, Tomoyuki, Kakutani, Shigenori, Tokunaga, Mayuko, Uemura, Yukari, Sato, Yusuke, Enomoto, Yutaka, Nishimatsu, Hiroaki, Fujimura, Tetsuya, Fukuhara, Hiroshi, Takahashi, Satoru, Kume, Haruki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883255/
https://www.ncbi.nlm.nih.gov/pubmed/35210308
http://dx.doi.org/10.1136/jitc-2021-003965
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author Kawai, Taketo
Taguchi, Satoru
Nakagawa, Tohru
Kamei, Jun
Nakamura, Yu
Obinata, Daisuke
Yamaguchi, Kenya
Kaneko, Tomoyuki
Kakutani, Shigenori
Tokunaga, Mayuko
Uemura, Yukari
Sato, Yusuke
Enomoto, Yutaka
Nishimatsu, Hiroaki
Fujimura, Tetsuya
Fukuhara, Hiroshi
Takahashi, Satoru
Kume, Haruki
author_facet Kawai, Taketo
Taguchi, Satoru
Nakagawa, Tohru
Kamei, Jun
Nakamura, Yu
Obinata, Daisuke
Yamaguchi, Kenya
Kaneko, Tomoyuki
Kakutani, Shigenori
Tokunaga, Mayuko
Uemura, Yukari
Sato, Yusuke
Enomoto, Yutaka
Nishimatsu, Hiroaki
Fujimura, Tetsuya
Fukuhara, Hiroshi
Takahashi, Satoru
Kume, Haruki
author_sort Kawai, Taketo
collection PubMed
description BACKGROUND: Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias. METHODS: The study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis. RESULTS: Of the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (−) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1–2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1–2 irAEs as independent favorable prognostic factors for OS and CSS. CONCLUSION: Even after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1–2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.
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spelling pubmed-88832552022-03-17 Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis Kawai, Taketo Taguchi, Satoru Nakagawa, Tohru Kamei, Jun Nakamura, Yu Obinata, Daisuke Yamaguchi, Kenya Kaneko, Tomoyuki Kakutani, Shigenori Tokunaga, Mayuko Uemura, Yukari Sato, Yusuke Enomoto, Yutaka Nishimatsu, Hiroaki Fujimura, Tetsuya Fukuhara, Hiroshi Takahashi, Satoru Kume, Haruki J Immunother Cancer Immunotherapy Biomarkers BACKGROUND: Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias. METHODS: The study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis. RESULTS: Of the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (−) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1–2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1–2 irAEs as independent favorable prognostic factors for OS and CSS. CONCLUSION: Even after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1–2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment. BMJ Publishing Group 2022-02-24 /pmc/articles/PMC8883255/ /pubmed/35210308 http://dx.doi.org/10.1136/jitc-2021-003965 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Kawai, Taketo
Taguchi, Satoru
Nakagawa, Tohru
Kamei, Jun
Nakamura, Yu
Obinata, Daisuke
Yamaguchi, Kenya
Kaneko, Tomoyuki
Kakutani, Shigenori
Tokunaga, Mayuko
Uemura, Yukari
Sato, Yusuke
Enomoto, Yutaka
Nishimatsu, Hiroaki
Fujimura, Tetsuya
Fukuhara, Hiroshi
Takahashi, Satoru
Kume, Haruki
Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title_full Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title_fullStr Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title_full_unstemmed Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title_short Impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
title_sort impact of immune-related adverse events on the therapeutic efficacy of pembrolizumab in urothelial carcinoma: a multicenter retrospective study using time-dependent analysis
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883255/
https://www.ncbi.nlm.nih.gov/pubmed/35210308
http://dx.doi.org/10.1136/jitc-2021-003965
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