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Prognostic models could guide treatment for advanced urothelial cancer
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Six clinical factors may assist clinicians in the appropriate use of atezolizumab among patients with advanced urothelial cancer, according to post hoc study results scheduled for presentation at the Genitourinary Cancers Symposium.
“Fortunately, we’ve had five new checkpoint inhibitors approved by the FDA in the last couple of years but, at this time, we don’t know which therapy to give to each individual patient,” Gregory Pond, PhD, associate professor of oncology at McMaster University in Hamilton, Ontario, said during a press cast. “Prognostic models will help us identify which patients might benefit the most from which therapy.”
Urothelial cancers typically occur in the urinary system, and bladder cancers account for the majority of cases. An estimated 81,190 new diagnoses of bladder cancer and 17,240 deaths will occur in the United States in 2018.
To develop a prognostic model, researchers analyzed data from two clinical trials of PD-L1 inhibitor atezolizumab (Tecentriq, Genentech) among patients with advanced urothelial cancer that worsened despite cisplatin chemotherapy. Researchers developed the model based on data from 310 patients enrolled in the phase 2 IMvigor210 trial, and they validated it based on data from the phase 1 PCD4989g trial of 95 patients with bladder cancer.
Researchers considered various clinical factors that previously predicted survival for patients with advanced bladder cancer receiving chemotherapy, including performance status, primary tumor site, sites of metastases, stage at diagnosis, various blood test results, smoking status and prior therapies. In addition, researchers assessed PD-L1 status of immune cells, which is a marker for efficacy of atezolizumab.
The six factors included in the optimal prognostic model for OS included:
- ECOG performance status (HR = 1.64; 95% CI, 1.2-2.24);
- metastasis to the liver (HR = 1.45; 95% CI, 1.08-1.94);
- elevated blood platelet count (HR = 1.73; 95% CI, 1.14-2.61);
- increased neutrophil-lymphocyte ratio (HR = 1.84; 95% CI, 1.45-2.34);
- elevated lactate dehydrogenase level (HR = 1.54; 95% CI, 1.19-1.99); and
- anemia (HR = 1.6; 95% CI, 1.17-2.21).
Researchers associated patient survival with the number of prognostic factors a patient reported. In the Imvigor210 trial, the median OS was 19.6 months for those with one or fewer factors, 5.9 months for those with two to three factors, and 2.6 months for those with four or more factors. Researchers noted their model needs further validation and refinement.
“We’ve developed a prognostic model for OS, which is now proposed for patients with advanced urothelial carcinoma receiving postplatinum atezolizumab and it consists of six variables,” Pond said. “The initial results of our study are very promising in both the training and validation datasets. We need to evaluate how the model performs in larger sample sizes and how it works with other checkpoint inhibitors.” – by Chuck Gormley
Disclosures: Genentech provided data for the study. Pond reports an immediate family member is employed by Roche Canada. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Sumanta K. Pal, MD
Although there is no doubt that the introduction of immunotherapy represents a major breakthrough in bladder cancer management, it is really important to bear in mind that a minority of patients — typically one quarter or less — will have substantial tumor shrinkage with these therapies. There also is a relatively small proportion of patients who will have extended survival with these treatments. Until the results of this study, there was no way to easily discern prognosis and identify who might benefit most.
This easily applied score developed by Pond and colleagues — based on parameters readily available on a patient’s chart — provides tremendous input. Although I would not necessarily withhold therapy on the basis of an anticipated poor prognosis, I would consider using this information to counsel patients who want to be better informed of potential outcomes with immunotherapy. Of note, there are multiple studies applying combinations of chemotherapy with immunotherapy that have yet to report in advanced bladder cancer.
Further, studies are ongoing to assess combinations of immune therapy in the same setting. If these studies are positive, there would be a massive paradigm shift in how we manage advanced bladder cancer. At that point in time we would have to determine if the model established by Pond and colleagues would remain relevant in that climate.
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