Abstract
Background: In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses. Patients and Methods: Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival. Results: The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell’s C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37). Conclusion: Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.
- Pembrolizumab
- urothelial cancer
- neutrophil-lymphocyte ratio
- NLR
- lactate dehydrogenase
- LDH
- C-reactive protein
- CRP
- immune checkpoint inhibitor
- predictive factor
- Received February 6, 2022.
- Revision received February 27, 2022.
- Accepted March 2, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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