Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

• Published in: Cancer medicine (Malden, MA) Vol. 10; no. 10; pp. 3188 - 3196
• Main Authors: Ito, Katsuhiro, Kobayashi, Takashi, Kojima, Takahiro, Hikami, Kensuke, Yamada, Takeshi, Ogawa, Kosuke, Nakamura, Kenji, Sassa, Naoto, Yokomizo, Akira, Abe, Takashige, Tsuchihashi, Kazunari, Tatarano, Shuichi, Inokuchi, Junichi, Tomida, Ryotaro, Fujiwara, Maki, Takahashi, Atsushi, Matsumoto, Kazumasa, Shimizu, Kosuke, Araki, Hiromasa, Kurahashi, Ryoma, Osaki, Yu, Tashiro, Yu, Uegaki, Masayuki, Ogawa, Osamu, Kitamura, Hiroshi, Nishiyama, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2021; John Wiley and Sons Inc; Wiley
• Subjects: Bladder cancer; Chemotherapy; Clinical Cancer Research; Clinical trials; Hemoglobin; Immunotherapy; Leukocytes (neutrophilic); Liver; Lymphocytes; Medical prognosis; Metastases; Metastasis; Monoclonal antibodies; Multivariate analysis; Neutrophils; Oncology; Original Research; Pembrolizumab; performance status; Response rates; Risk factors; Targeted cancer therapy; transitional cell carcinoma; Trends; Urothelial carcinoma; Japan; pembrolizumab; performance status; urothelial carcinoma; transitional cell carcinoma; bladder cancer; immunotherapy
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3863

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. Among patients who received pembrolizumab to treat urothelial carcinoma, those with Eastern Cooperative Oncology Group performance status ≥2 exhibited worse overall response rates and overall survival than those with performance status ≤1 despite their comparable safety profiles. Among the patients with impaired performance status, those with a neutrophil–lymphocyte ratio <3.5 and no liver metastases may most greatly benefit from pembrolizumab.