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SAN FRANCISCO-Researchers have developed a model to predict overall survival for people with advanced urothelial cancers treated with the immune checkpoint inhibitor atezolizumab. The model, which is based on six clinical factors, may help inform treatment decisions for use of atezolizumab in these patients. These findings were presented at the 2018 Genitourinary Cancers Symposium (Abstract 413).

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"In just the past few years, the FDA has approved five new immunotherapies for urothelial cancers," said lead study author Gregory Pond, PhD, Associate Professor, McMaster University, Hamilton, Ontario, Canada. "Based on the rapid availability of new therapies, we thought it was important to try to assess which patients might benefit the most from atezolizumab, which is one type of these new therapies. We believe we've developed the first prognostic model that, once confirmed in larger studies, could provide a critical decision-making tool for clinicians."


Study Details

Urothelial cancers typically occur in the urinary system, and bladder cancers account for the majority of urothelial cancers; other types include ureter and renal pelvis cancers. An estimated 81,190 new diagnoses of bladder cancer will occur in the U.S. in 2018, and there will be an estimated 17,240 deaths, according to the American Cancer Society.


To develop the model, the researchers analyzed data from two clinical trials of PD-L1 inhibitor atezolizumab in people with advanced urothelial cancer that worsened despite cisplatin chemotherapy, which is the standard treatment for this disease. The model was developed based on data from 310 people enrolled in the phase II IMvigor210 trial, and then validated based on data from a phase I trial of 95 people with bladder cancer (PCD4989g).


Key Findings

Researchers considered various clinical factors that had been previously shown to predict survival in patients with advanced bladder cancer receiving chemotherapy, including performance status, the site of the primary tumor and sites of metastases, stage at diagnosis, various blood test results, smoking status, and prior therapies. In addition, they assessed PD-L1 status of immune cells, which is a marker for efficacy of atezolizumab.


The six factors that were ultimately included in the optimal prognostic model for overall survival were:


1. ECOG performance status;


2. metastasis to the liver;


3. elevated blood platelet count;


4. increased neutrophil-lymphocyte ratio;


5. elevated lactate dehydrogenase level; and


6. anemia.



The researchers found that patient survival was associated with the number of prognostic factors a patient had. In the Imvigor210 trial, the median overall survival was 19.6 months for those with 0-1 factors, 5.9 months for those with 2-3 factors, and 2.6 months for those with four factors or more.


Next Steps

"While other factors also affect overall survival, no others were observed to be statistically significant in this dataset," Pond noted. "That is also why further validation of this model is required, as we will need to check if the factors identified in this model are consistent across different datasets."


The authors also hope to do some subgroup analyses to determine if people with specific characteristics may benefit more from atezolizumab immunotherapy than others. More research is also needed to determine if this prognostic model could be applied to other patient populations or other immunotherapies.


"Advances in immunotherapy have come quite quickly over the past decade, and we've had tremendous success treating many previously difficult-to-treat cancers, such as bladder cancer," said ASCO Expert Sumanta K. Pal, MD, Assistant Clinical Professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, Duarte, Calif. "It's important to remember, however, that it is the minority of patients who have long-term responses to these therapies, and we currently have no means of pinpointing who these patients are. As this study demonstrates, prognostic models may help us apply immunotherapy to patients who stand to derive the most benefit."