Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single‐center analysis in Japan

Abstract

Background: The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab. Aim:We investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real-world clinical practice. Methods and results:The medical records of 74 consecutive Japanese patients with metastatic urothelial cancer (UC), who started pembrolizumab as a secondor later-line treatment at our institution between January 2018 and March 2020, were reviewed and statistically analyzed. The median follow-up period after initiation of pembrolizumab was 8.5 (interquartile range: 3.5-15.7) months.The objective response rate was 30.2%, the median progression-free survival period was 4.9 months, and the median overall survival (OS) period was 13.3 months. Evaluation revealed that 39 (52.9%) patients experienced adverse events (AEs), among whom eight patients (10.9%) had severe AEs (grade 3 or more), including grade 5 hemophagocytic syndrome. Multivariate analysis indicated that the presence of liver metastasis, worse performance status (≥2), elevated serum lactate dehydrogenase, and increased C-reactive protein were predictive of shorter OS. Conclusion:We studied the effectiveness and safety profile of pembrolizumab therapy in Japanese UC patients. We believe that the data presented here will be useful for clinical physicians.

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

“…The survival benefit of immunotherapy in both untreated and pretreated patients with mUC has been observed regardless of all of those clinical factors, confirming their prognostic but not predictive value, in many retrospective analyses [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ] and subgroup and post-hoc analyses of prospective randomised trials [ 71 , 72 ].…”

Impact of C-reactive Protein Flare Response in Patients With Advanced Urothelial Carcinoma Who Received Pembrolizumab

“…In this study, though favorable ORR, OS, and PFS were observed in patients with a CRP flare response, it was not possible to reveal the differences in oncological outcomes between flare-responder and responder groups using multivariable analysis because of the small number of patients and absence of progression or death in patients with a CRP flare response during the study period. However, patient backgrounds including the factors associated with treatment efficacy (3)(4)(5)(6)(7)(8)17) among each group were not significantly different, and the CRP flare response might be an important factor to predict favorable oncological outcomes. In clinical practice, therefore, pembrolizumab should be continued in patients with a CRP flare response, when irAEs are manageable.…”

“…Recently, various biomarkers including blood cell count markers (11) or nutritional status-based markers such as prognostic nutritional index (12) were reported in pembrolizumab therapy for patients with advanced UC. Several studies on UC have reported that elevated CRP levels before surgery (13), chemotherapy (14,15), or ICIs treatment (3,7,8) were associated with poor prognosis.…”

“…Several predictive biomarkers have been identified in patients with advanced UC on pembrolizumab (3)(4)(5)(6)(7)(8). Markers related to systemic inflammatory factors, including C-reactive protein (CRP) (3,4,(6)(7)(8) or the neutrophile/lymphocyte ratio (5-7), were reported as useful. Previous studies showed CRP baseline levels (3,7,8) or kinetics (4,6) were associated with clinical outcomes.…”

“…Markers related to systemic inflammatory factors, including C-reactive protein (CRP) (3,4,(6)(7)(8) or the neutrophile/lymphocyte ratio (5-7), were reported as useful. Previous studies showed CRP baseline levels (3,7,8) or kinetics (4,6) were associated with clinical outcomes. Furthermore, temporary elevation of CRP levels followed by a decrease below baseline (CRP flare response) was also investigated as one of the biomarkers in patients with metastatic renal cell carcinoma (RCC) (9).…”