Abstract

A prognostic model for overall survival (OS) of post-platinum patients with metastatic urothelial carcinoma (mUC) receiving PD-1/PD-L1 inhibitors is necessary since existing models were constructed in the chemotherapy setting.Patient level data were used from phase I/II trials evaluating PD-L1 inhibitors following platinum-based chemotherapy for mUC. The derivation dataset consisted of 2 phase I/II trials evaluating atezolizumab (n=405). Two phase I/II trials that evaluated avelumab (n=242) and durvalumab (n=198) comprised the validation datasets. Cox regression analyses evaluated the association of candidate prognostic factors with OS. Stepwise selection was employed to select an optimal model using the derivation dataset. Discrimination and calibration were assessed in the avelumab and durvalumab datasets.The 5 prognostic factors identified in the optimal model employing the atezolizumab derivation dataset 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-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 datasets, respectively. A web-based interactive tool was developed to calculate the expected survival probabilities based on risk factors.A validated 5-factor model has satisfactory prognostic performance for survival across 3 PD-L1 inhibitors to treat mUC post-platinum and may assist in stratification, interpreting and designing trials incorporating PD-1/PD-L1 inhibitors in the post-platinum setting.

View details for DOI 10.1097/JU.0000000000001199

View details for PubMedID 32552295