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O'Donnell Discusses IMvigor Findings, Excitement Over Atezolizumab Approval in mUC

Gina Columbus @ginacolumbusonc
Published: Thursday, Jul 14, 2016

Peter O’Donnell, MD

Peter O’Donnell, MD

Following encouraging results of the phase II IMvigor 210 study, the FDA granted the PD-L1 inhibitor atezolizumab (Tecentriq) an accelerated approval in May 2016 as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC). The indication is for patients whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.

“It is a new paradigm,” explains Peter O’Donnell, MD. “Now, for patients in the postchemotherapy setting, we have another standard of care in an area where there really hadn’t been a second-line standard of care for decades.”

O’Donnell, an assistant professor of Medicine at the University of Chicago Medicine, discussed these findings and more in his lecture on refractory metastatic bladder cancer during the OncLive State of the Science Summit on GU and Prostate Cancer.

In an interview with OncLive during the meeting, O’Donnell discussed the encouraging IMvigor results, the impact of atezolizumab in the treatment landscape, and the role of immunotherapy in mUC.

OncLive: What should community oncologists understand about the advancements in refractory metastatic bladder cancer?

O’Donnell: It has been decades since we have really had any new therapies in the United States for metastatic bladder cancer. The past few years have been so exciting with the onset of these immunotherapy drugs in clinical trials, and now with the approval of atezolizumab for patients with platinum-refractory metastatic disease.

Immunotherapy is going to be paradigm changing; there is no doubt about that. Any of us who have used these drugs to treat patients with urothelial cancer know that, when it works, it is dramatic. It is not subtle when these patients begin responding, even in the first few weeks that they are on the drugs.

Then, what is really remarkable is the durable response in many patients, where they are living beyond 1 year in the post-platinum setting, which is just unheard of for this disease. There is not only clinical benefit for patients, but also a real disease-altering type of effect.

You were very much involved with the IMvigor study. Can you shed some light on that trial and discuss the significant findings?

It is a study of over 300 patients who were all treated with prior platinum-based therapy in the metastatic setting. All patients received atezolizumab once every 3 weeks as part of the schedule. What is notable from it is that, not only does it seem to really move the needle from what we would expect from a survival standpoint in patients that expressed PD-L1 specifically, but it also worked in a number of patients.

It passed the primary endpoint of the study as far as response rate, and the therapy was quite tolerable. Something that we are all familiar with is that patients are clambering to try to get these immunotherapies because they are even aware that, compared with chemotherapy, these drugs are really well tolerated. There is this 15% rate of grade 3 and 4 adverse events, but that is really acceptable compared with other therapies that we use for metastatic cancer.

What are some of those treatment-related adverse events? How do you best manage them?

The ones that really caught attention are these immune-related adverse events, which happen in 5% of patients at the grade 3 and 4 levels, so those are severe ones that we really need to be concerned about. It was a small number, but still notable. I have had patients who have had these severe, immune-related adverse events—pneumonitis, hepatitis, and colitis. One patient even had a case of a myositis where she was not able to even lift her arm above her shoulder; this is very rare, but striking and debilitating to these patients.

The good news is that, when those happen, they are generally manageable—meaning we withdraw the PD-L1 drug, give the patient steroids and, usually, within days, we see resolution or regression of the immune-related adverse events. Unfortunately, in most of these patients with that severe toxicity, it means they are probably not going to get the drug again. That is the hard part because, for a lot of these patients, it is helping them.

How will the FDA approval of atezolizumab impact the treatment landscape?

The use of other cytotoxics, which many oncologists try, really was not changing the landscape. It was not really extending survival in these patients. Now, there is a well-tolerated therapy that is clearly having durable activity—at least in a subset of patients.




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