Predicting Objective Response of Pembrolizumab in Platinum-Refractory Urothelial Carcinoma Based on Neutrophil-Lymphocyte Ratio Fluctuation and Liver Metastases

Oncology. 2024;102(6):457-464. doi: 10.1159/000534554. Epub 2023 Oct 13.

Abstract

Introduction: It is well known that patients with objective response to pembrolizumab have a durable duration of response, leading to favorable survival outcomes. We investigated the possibility of predicting the objective response with concise indicators obtained from daily clinical practice.

Methods: In our multi-institutional cohort, 220 platinum-refractory metastatic urothelial carcinoma (mUC) patients treated with pembrolizumab for at least 6 weeks with complete information of objective response were investigated.

Results: The median follow-up was 7.3 months, and 119 patients deceased during the follow-up. A multivariate logistic regression analysis exhibited two independent variables predicting the objective response, including the neutrophil-lymphocyte ratio (NLR) change at 6 weeks of treatment and liver metastasis. We proposed a risk group using these two indicators. Patients with no predictive indicators/one of those were assigned to favorable (42%)/intermittent (47%) risk groups. Patients with both indicators were assigned to poor risk (11%). Notably, the objective response rate was well delineated in 41%, 25%, and 0% for favorable-, intermediate-, and poor-risk groups, respectively (p < 0.001). Distinct overall survival (OS) between the risk groups was also confirmed with the median OS of 14.1, 11.7, and 4.2 months in favorable-, intermediate-, and poor-risk groups, respectively.

Conclusions: At the 6 weeks of the pembrolizumab treatment, our risk model predicts the objective response rate precisely. Notably, those classified as "poor risk" - marked by liver metastasis and an increased NLR - should be considered for alternative therapy with a different mode of action, highlighting a critical decision point in treatment optimization.

Keywords: Liver metastasis; Neutrophil-lymphocyte ratio; Pembrolizumab; Prediction; Urothelial carcinoma.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / secondary
  • Lymphocytes* / pathology
  • Male
  • Middle Aged
  • Neutrophils* / pathology
  • Retrospective Studies
  • Treatment Outcome
  • Urologic Neoplasms / blood
  • Urologic Neoplasms / drug therapy
  • Urologic Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • Antineoplastic Agents, Immunological