Five-Factor Prognostic Model for Survival of Post-Platinum Patients with Metastatic Urothelial Carcinoma Receiving PD-L1 Inhibitors.

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.

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.

• Authors: Guru Sonpavde, Juliane Manitz, Chen Gao, Darren Tayama, Constanze Kaiser, Daniel Hennessy, Doris Makari, Ashok Gupta, Shaad Essa Abdullah, Guenter Niegisch, Jonathan E Rosenberg, Dean F Bajorin, Petros Grivas, Andrea B Apolo, Robert Dreicer, Noah M Hahn, Matthew D Galsky, Andrea Necchi, Sandy Srinivas, Thomas Powles, Toni K Choueiri, Gregory R Pond
• Journal: The Journal of urology (J Urol) Vol. 204 Issue 6 Pg. 1173-1179 (12 2020) ISSN: 1527-3792 [Electronic] United States
• PMID: 32552295 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• Carboplatin
• Cisplatin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Immunological (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• B7-H1 Antigen (antagonists & inhibitors, immunology)
• Carboplatin (pharmacology, therapeutic use)
• Carcinoma, Transitional Cell (drug therapy, mortality, secondary)
• Cisplatin (pharmacology, 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
• Nomograms
• Risk Assessment (methods)
• Time Factors
• Urologic Neoplasms (drug therapy, mortality, pathology)