Re: Five-factor Prognostic Model for Survival of Post-platinum Patients with Metastatic Urothelial Carcinoma Receiving PD-L1 Inhibitors

Autor: Andrea Necchi, Daniel Hennessy, Juliane Manitz, Toni K. Choueiri, Noah M. Hahn, Shaad Essa Abdullah, Chen Gao, Constanze Kaiser, Ashok K. Gupta, Sandy Srinivas, Andrea B. Apolo, Jonathan E. Rosenberg, Darren Tayama, Doris Makari, Gregory R. Pond, Guru Sonpavde, Dean F. Bajorin, Matthew D. Galsky, Thomas Powles, Petros Grivas, Robert Dreicer, Guenter Niegisch
Přispěvatelé: Sonpavde, G., Manitz, J., Gao, C., Tayama, D., Kaiser, C., Hennessy, D., Makari, D., Gupta, A., Abdullah, S. E., Niegisch, G., Rosenberg, J. E., Bajorin, D. F., Grivas, P., Apolo, A. B., Dreicer, R., Hahn, N. M., Galsky, M. D., Necchi, A., Srinivas, S., Powles, T., Choueiri, T. K., Pond, G. R.
Rok vydání: 2021
Předmět:
Oncology
Male
Time Factors
030232 urology & nephrology
Datasets as Topic
Kaplan-Meier Estimate
carcinoma
B7-H1 Antigen
Carboplatin
neoplasm metastasis
0302 clinical medicine
Antineoplastic Agents
Immunological
Antineoplastic Combined Chemotherapy Protocols
platinum
Immune Checkpoint Inhibitors
Aged
80 and over
biology
Clinical Trials
Phase I as Topic
Middle Aged
Prognosis
drug therapy
transitional cell
Female
Adult
medicine.medical_specialty
Urologic Neoplasms
Metastatic Urothelial Carcinoma
Urology
MEDLINE
Risk Assessment
Article
03 medical and health sciences
Pharmacotherapy
Clinical Trials
Phase II as Topic
Internal medicine
PD-L1
medicine
Overall survival
Carcinoma
Humans
Aged
Neoplasm Staging
Platinum
Carcinoma
Transitional Cell
business.industry
medicine.disease
Nomograms
Urinary Bladder Neoplasms
Prognostic model
biology.protein
prognosis
Cisplatin
business
Zdroj: J Urol
ISSN: 1873-7560
Popis: 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. 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. 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. 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.
Databáze: OpenAIRE
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