Katsuhiro Ito1,2,3, Takashi Kobayashi1,4, Takahiro Kojima5, Kensuke Hikami6, Takeshi Yamada7, Kosuke Ogawa8, Kenji Nakamura9, Naoto Sassa10, Akira Yokomizo11, Takashige Abe12, Kazunari Tsuchihashi13, Shuichi Tatarano14, Junichi Inokuchi15, Ryotaro Tomida16, Maki Fujiwara17, Atsushi Takahashi18, Kazumasa Matsumoto19, Kosuke Shimizu20, Hiromasa Araki3, Ryoma Kurahashi21, Yu Osaki22, Yu Tashiro23, Masayuki Uegaki24, Osamu Ogawa1,4, Hiroshi Kitamura25, Hiroyuki Nishiyama5. 1. Department of Urology, Kyoto University Hospital, Kyoto, Japan. 2. Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan. 3. Department of Urology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan. 4. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 5. Department of Urology, University of Tsukuba, Ibaraki, Japan. 6. Department of Urology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan. 7. Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 8. Department of Urology, Kobe City Nishi-Kobe Medical Center, Hyogo, Japan. 9. Department of Urology, Japanese Red Cross Osaka Hospital, Osaka, Japan. 10. Department of Urology, Nagoya University, Aichi, Japan. 11. Department of Urology, Harasanshin Hospital, Fukuoka, Japan. 12. Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 13. Department of Urology, Japanese Red Cross Otsu Hospital, Shiga, Japan. 14. Department of Urology, Kagoshima University, Kagoshima, Japan. 15. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 16. Department of Urology, Shikoku Cancer Center, Ehime, Japan. 17. Department of Urology, Tenri Hospital, Nara, Japan. 18. Department of Urology, Hakodate Goryoukaku Hospital, Hokkaido, Japan. 19. Department of Urology, Kitasato University, Kanagawa, Japan. 20. Department of Urology, Kyoto Katsura Hospital, Kyoto, Japan. 21. Department of Urology, Kumamoto University, Kumamoto, Japan. 22. Department of Urology, National Hospital Organization Himeji Medical Center, Hyogo, Japan. 23. Department of Urology, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan. 24. Department of Urology, Toyooka Hospital, Hyogo, Japan. 25. Department of Urology, Toyama University, Toyama, Japan.
Abstract
BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.
BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.