Clinical Trial Highlights Poor Prognosis for Bladder Cancer Patients

Analysis of the IMvigor 210 clinical trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma (the most common type of bladder cancer) who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker that may aid in development of personalized treatment of the disease.

Results of the IMvigor 210 study prompted the [U.S.] Food and Drugs Administration to approve atezolizumab for use as a treatment for bladder cancer. Atezolizumab is an Fc‐engineered, humanized, monoclonal antibody that binds to programmed death‐ligand 1 (PD‐L1) and inhibits its interactions with the PD‐1 and B7.1 receptors. This releases the PD‐L1/PD‐1 mediated inhibition of the immune response, including reactivation of the anti‐tumor immune response.

Investigators at Baylor College of Medicine (Houston, TX, USA) developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. The Cancer Genome Atlas is a project begun in 2005 that used genome sequencing and bioinformatics to catalogue genetic mutations responsible for cancer.

The investigators identified 11 patients with a "neuronal" subtype, with a 100% response rate in eight confirmed cases (two complete response, six partial response), and 72% overall, including three of 11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which has a distinct expression profile and is associated with poor survival and less favorable outcomes.

"Of the 11 patients we identified as having a neuronal subtype, all of those evaluable for objective response responded to the treatment (two complete response, six partial response), or 72% overall. This translated to a very high survival probability which is unprecedented in advanced bladder cancer," said senior author Dr. Seth Paul Lerner, professor of urology at Baylor College of Medicine. "Although this is a small group of patients, it is very exciting to see that our basic research can be directly translated to the clinical setting allowing us to determine which subtype of bladder cancer has a better chance to respond well to a specific treatment. We were able to show that mutation signatures, molecular subtypes, load of new cancer-associated molecules, and known clinical and pathological factors have a very clear influence on overall patient survival. But, how can we apply this knowledge into clinical practice?"

"One of the challenges that we have when taking care of patients with bladder cancer is that from one patient to the next, the prognosis, the stage, and the response to different kinds of treatment differ," said Dr. Lerner. "The diverse cancer characteristics pose a challenge when selecting the best treatment for each patient."

The study was published in the March 7, 2019, online edition of the journal European Urology.

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