ASCO GU 2018: New 6-factor prognostic model for patients with advanced urothelial carcinoma receiving post-platinum atezolizumab

San Francisco, CA ( The introduction of checkpoint inhibitors as a second line agent has been a game changer in the treatment of urothelial carcinoma patients. Following landmark results of the Keynote-045, the FDA has now approved of four other PD-1 and PD-L1 inhibitors. While some of these checkpoint inhibitors have validated the results of Keynote-045, some others have shown contradictory results (IMvigor210) leading some experts to wonder if the differences are patient related. A team of investigators involved with IMvigor210 have decided to use the available data from the trial to identify key predictive characteristics that may impact response and ultimately overall survival (0S) in UC patients who have failed platinum chemotherapy.  

Using patient and survival data from the IMvigor210 trial, the authors performed univariate and multivariate Cox regression analyzes to identify prognostic factors for OS.  A stepwise selection approach was used to identify an optimal model. The model was then validated using patient and survival data obtained from the PCD4869g phase I clinic trial, consisting of 95 pretreated metastatic bladder cancer patients who also received atezolizumab. The model consisted of 6-factors: Neutrophil to Lymphocyte Ratio (NLR) ≥ 5, ECOG-PS ≥ 1, Platelet level ≥ 400 109/L, Hgh < 10 g/dL, LDH level ≥ 280 U/L and presence of liver metastases. The C-Index for the training dataset was 0.690 and 0.759 for the validation set. Interestingly, tumor PD-L1 level was not associated with OS in either the training or validation sets. On survival analysis, increasing number of factors was associated with worsening overall survival in both the discovery (0-1: 19.6; 2-3: 5.9; 4+: 2.8 months) and training sets (0-1: 19.4; 2-3: 7.2; 4+: 2.6 months). 

In summary, a prognostic model for OS has been introduced for patients with advanced urothelial carcinoma receiving post-platinum atezolizumab. The model consists of 6-factors which include a measure of performance status, the presence of liver metastases along with other hematological factors. The model appears promising in predicting OS in both the training and validation sets. Further validation in larger cohorts and in those treated with other checkpoint inhibitors will be required prior to its implementation into clinical practice. 

Presented by: Speaker: Gregory R. Pond, Ph.D., McMaster University, Hamilton, Ontario Canada 

Written by: Andres F. Correa, MD, Fox Chase Cancer Center-TempleHealth, Philadelphia, PA, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

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