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Five-Factor Prognostic Model for Survival of Post-Platinum Patients with Metastatic Urothelial Carcinoma Receiving PD-L1 Inhibitors.
- Source :
-
The Journal of urology [J Urol] 2020 Dec; Vol. 204 (6), pp. 1173-1179. Date of Electronic Publication: 2020 Jun 18. - Publication Year :
- 2020
-
Abstract
- Purpose: A prognostic model for overall survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-1/PD-L1 inhibitors is necessary as existing models were constructed in the chemotherapy setting.<br />Materials and Methods: Patient level data were used from phase I/II trials evaluating PD-L1 inhibitors following platinum based chemotherapy for metastatic urothelial carcinoma. The derivation data set consisted of 2 phase I/II trials evaluating atezolizumab (405). Two phase I/II trials that evaluated avelumab (242) and durvalumab (198) comprised the validation data sets. Cox regression analyses evaluated the association of candidate prognostic factors with overall survival. Stepwise selection was used to select an optimal model using the derivation data set. Discrimination and calibration were assessed in the avelumab and durvalumab data sets.<br />Results: The 5 prognostic factors identified in the optimal model using the atezolizumab derivation data set were ECOG-PS (1 vs 0, HR 1.80, 95% CI 1.36-2.36), liver metastasis (HR 1.55, 95% CI 1.20-2.00), platelet count (HR 2.22; 95% CI 1.54-3.18), neutrophil-to-lymphocyte ratio (HR 1.94, 95% CI 1.57-2.40) and lactate dehydrogenase (HR 1.60, 95% CI 1.28-1.99). There was robust discrimination of survival between low, intermediate and high risk groups. The c-statistic was 0.692 in the derivation and 0.671 and 0.773 in the avelumab and durvalumab validation data sets, respectively. A web based interactive tool was developed to calculate the expected survival probabilities based on risk factors.<br />Conclusions: A validated 5-factor model has satisfactory prognostic performance for survival across 3 PD-L1 inhibitors to treat metastatic urothelial carcinoma after platinum therapy and may assist in stratification, interpreting and designing trials incorporating PD-1/PD-L1 inhibitors in the post-platinum setting.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological pharmacology
Antineoplastic Combined Chemotherapy Protocols pharmacology
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen immunology
Carboplatin pharmacology
Carboplatin therapeutic use
Carcinoma, Transitional Cell mortality
Carcinoma, Transitional Cell secondary
Cisplatin pharmacology
Cisplatin therapeutic use
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Datasets as Topic
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
Risk Assessment methods
Time Factors
Urologic Neoplasms mortality
Urologic Neoplasms pathology
Antineoplastic Agents, Immunological therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Carcinoma, Transitional Cell drug therapy
Nomograms
Urologic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3792
- Volume :
- 204
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of urology
- Publication Type :
- Academic Journal
- Accession number :
- 32552295
- Full Text :
- https://doi.org/10.1097/JU.0000000000001199