Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

Abstract

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

“…Some efficacy of bone-modifying agents, such as zoledronic acid or denosumab, has been reported for SREs, but it is not sufficient [ 14 ]. Although the research direction of ICIs for ur/mUC is scattered, there are few reports focusing on bone metastasis, and it may be difficult to evaluate because other therapeutic modalities, such as radiation therapy, may be added [ 13 , 15 , 16 ]. The advent of pembrolizumab has not led to significant progress in the treatment of bone metastasis ( Figure 2 ), and treatment and maintenance of the QOL of patients with UC-related bone metastases should be investigated further in the future.…”

Tertiary lymphoid structure and neutrophil–lymphocyte ratio coordinately predict outcome of pembrolizumab

“…However, the efficacy of these therapies is not uniform across all patients, necessitating the identification of reliable predictive biomarkers to guide treatment decisions and optimize clinical outcomes. 17 NLR in peripheral blood is a cost-effective and widely accessible biomarker significantly associated with survival outcomes and response rates following CPIs treatment across multiple cancer types. 9 Interestingly, a previous study showed that the prognostic value of NLR appears to be enhanced when combined with TMB, another established biomarker of response to CPIs.…”

Efficacy of pembrolizumab and comprehensive CD274/PD-L1 profiles in patients previously treated with chemoradiation therapy as radical treatment in bladder cancer

“…Follow-up protocol was described in the previous report. 8 Briefly, follow-up CT for detecting any findings suspected of disease progression was scheduled every 6 weeks during the follow-up, and treatment response of pembrolizumab was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1. 15 Re-evaluation using MRI, bone scintigraphy, and positron emission tomography/CT (PET/CT) were further performed when necessary for the definitive diagnosis of immune-confirmed disease progression.…”

“… 7 Since then, pembrolizumab has been widely used in large numbers of patients worldwide as well as in Japan. 8 9 …”