Atezolizumab limits disease progression for metastatic urothelial bladder cancer

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Published: 30 Sep 2015
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Dr Jonathan E. Rosenberg - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Rosenberg discusses data he presented at ECC 2015 demonstrating that the investigational immunotherapy atezolizumab may prevent progression of metastatic urothelial bladder cancer in all age groups by 2.1 months.

This phase II, open-label study (IMvigor 210) is the first trial of its kind in metastatic bladder cancer to show that inhibiting PD-L1 increases the activity of the immune system to prevent disease progression and may improve patient survival in a heavily pre-treated population.

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ecancer's filming at ECC 2015 has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

 

ECC 2015

Atezolizumab limits disease progression for metastatic urothelial bladder cancer

Dr Jonathan E. Rosenberg - Memorial Sloan Kettering Cancer Center, New York, USA


Jonathan Rosenberg, you’re from Memorial Sloan Kettering. Tell me about your unit and what you’re doing there, first.

So I focus on treatment of advanced bladder cancer, developing novel therapies.

And you’ve got a novel therapy here, a new monoclonal antibody, and it’s an anti-PD-L1. Tell me about that, please. Why did you look at this checkpoint inhibition process?

So in bladder cancer we know that immune therapy has a long history of benefit in non-muscle invasive disease where patients are treated with things like BCG. Extending this into metastatic disease is a natural process. The phase Ia study that had been previously done with this drug, atezolizumab, showed dramatic responses in a subset of patients and that laid the groundwork to pursue this phase II study.

This is for patients with locally advanced or metastatic urothelial cancers. What happened, how many were there in the first study?

311 patients were treated on the clinical trial, they had locally advanced or metastatic disease and they all had to have had prior platinum chemotherapy. They had all been required to submit tissue for PD-L1 testing up front but the investigators and the patients weren’t privy to the results. We did show that there was an increase in proportion of responders with higher PD-L1 expression levels but that regardless, even in the absence of PD-L1 expression, you still saw responses.

So what was the size of the signal to this new drug, the anti-PD-L1 drug and how much did that differ when you got the biomarker indicating sensitivity?

All comers, 15% of patients had objective responses. Historically in bladder cancer chemotherapy in a heavily pre-treated population works in 5-10% of patients. So this, even at that level, is an improvement. When you have a high level of PD-L1 expression you had 27% of confirmed objective responses.

Could you put that into clinical context for me in the potential use of this new drug by cancer doctors?

So this is a relatively non-toxic treatment for a patient population that is quite frail, that doesn’t have a lot of options. In fact, there’s no approved drugs outside of the EU for advanced bladder cancer after failure of platinum therapies. So, regardless of your PD-L1 status, people did respond but there were more of them in the PD-L1 positive population. As time goes on and the data matures we’ll get a better sense because many of the patients who might still be able to respond haven’t yet responded. So these numbers may actually go up over time.

So what should doctors be taking home from this right now?

We have shown that this is an active drug in advanced bladder cancer. This is a second, third, fourth and fifth line study and so even though the response rates are on the lower end we still think that this is a highly active agent in a very heavily pre-treated population. I think it’s likely to lead to a drug approval in the next several years.

Thank you very much.

Thank you.