Association Between the Occurrence and Spectrum of Immune-Related Adverse Events and Efficacy of Pembrolizumab in Asian Patients With Advanced Urothelial Cancer: Multicenter Retrospective Analyses and Systematic Literature Review |
| |
| Authors: | Toshiki Kijima Hiroshi Fukushima Shota Kusuhara Hajime Tanaka Soichiro Yoshida Minato Yokoyama Junichiro Ishioka Yoh Matsuoka Noboru Numao Yasuyuki Sakai Kazutaka Saito Nobuaki Matsubara Takeshi Yuasa Hitoshi Masuda Junji Yonese Yukio Kageyama Yasuhisa Fujii |
| |
| Affiliation: | 1. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA;2. Google, Mountain View, CA;3. University of California, San Francisco, Department of Urology, Center for Digital Health Innovation, San Francisco, CA;4. The Ohio State University, Department of Urology, Columbus, OH;5. The Ohio State University, Department of Medicine, Columbus, OH;6. The Ohio State University, Department of Surgery, Columbus, OH;7. University of Texas Health Science Center at San Antonio, Department of Urology;1. Department of Surgery, McGill University Health Centre, Montreal, QC, Canada;2. Department of Oncology, McGill University, Montreal, QC, Canada;1. Department of Radiation Oncology, LAC+USC Medical Center, Los Angeles, CA;2. USC Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA;3. Department of Radiation Oncology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA |
| |
| Abstract: | An association between the development of overall or specific immune-related adverse events (irAEs) and outcomes of immune checkpoint inhibitors has recently been suggested. To address this emerging association in patients with urothelial cancer receiving pembrolizumab, we conducted a multicenter retrospective analysis, which is the first and largest in an Asian cohort as well as a systematic literature review. We retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab as second- or later-line treatment between January 2018 and March 2019. irAEs were categorized by the involved organs and graded using Common Terminology Criteria for Adverse Events version 5.0. Associations between irAEs and pembrolizumab efficacy, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. In our review of the literature, 28 studies, including 9 studies involving patients with urothelial cancer and 19 studies reporting the association between outcomes and spectrum of irAEs, were analyzed. Patients with irAEs had significantly higher ORR (52% vs. 16%, P < .01), longer PFS (11.0 months vs. 3.6 months, P < .01) and OS (median not reached vs. 13.1 months, P = .12) than in patients without irAEs. Endocrine (P = .02), pneumological (P = .06), and other (gastrointestinal, hematological, hepatic) (P = .04) irAEs were associated with increased ORR, whereas skin irAEs were not. Endocrine irAEs (P = .04) was associated with improved OS, whereas pneumological and skin irAEs were not. The association between the occurrence of irAEs and clinical efficacy of immune checkpoint inhibitors was consistently supported by the multiple studies we reviewed. The association between clinical outcomes and the spectrum of organs/systems affected by irAEs seems to be inconsistent and could be dependent on tumor type. irAEs were associated with a higher ORR and better survival of patients with advanced urothelial cancer treated with pembrolizumab. |
| |
| Keywords: | Immuno-oncology drug Overall survival Prognostic factor Progression-free survival System/organ involved |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
