Robert Dreicer, MD
If approved by the FDA for the treatment of patients with metastatic urothelial carcinoma (mUC), the PD-L1 inhibitor atezolizumab would shift the treatment landscape in the disease overnight, according to Robert Dreicer, MD.
Atezolizumab was granted a priority review by the FDA in March 2016, based on promising phase II findings from the IMvigor 210 trial, in which atezolizumab demonstrated an overall response rate of 15% in patients with locally advanced or metastatic disease. The FDA will make its approval decision by September 12, 2016.
“Basically, what you have is a therapeutic in a disease that hasn’t seen an approved drug since the mid-1990s in the United States, where you have unequivocal activity with reasonably good safety and, in those patients who respond, some of those responses are very durable,” says Dreicer. “That is a pretty compelling story in a disease that has not had any developments in therapy for 20-plus years.”
In an interview with OncLive
, Dreicer, professor, Division of Hematology/Oncology, University of Virginia Health System, provides insight on the IMvigor 210 study and how atezolizumab will dramatically change the treatment paradigm for patients with metastatic urothelial carcinoma, who have a severe unmet need.
OncLive: Can you provide an overview of the IMvigor 210 study?
: This was a large phase II clinical trial with 2 cohorts. The cohort presented at the 2016 AUA Annual Meeting was “cohort 2,” which consists of platinum-refractory patients with locally advanced or metastatic disease. All patients received atezolizumab intravenously at the same dosing schedule every 3 weeks. The primary endpoint of the trial was objective response, while secondary endpoints were progression-free survival, overall survival, safety, etc.
“Cohort 1,” which will be presented at the 2016 ASCO Annual Meeting, consisted of patients who were not fit for platinum-based therapy upfront. It’s a small number of patients, and that data are not yet in the public domain, so there is not yet much to say about it.
What is the significance of the reported findings?
There is unequivocal activity of an anti–PD-L1 monoclonal antibody in heavily pretreated patients with mUC. There is no question that those patients respond.
Although there was more activity in patients who more heavily expressed PD-L1 in their tumors, there was still activity and responses seen in patients who did not harbor any PD-L1 expression. Therefore, there is a range of activity in those patients who responded. Many of the responses were very durable and lasted many months.
Seeing as there were responses regardless of PD-L1 expression, what does this mean for using PD-L1 as a biomarker?
The reality is that, in many solid tumors that we’re treating, we have a little bit of sudden diversity. In the findings that led to the approval of nivolumab (Opdivo) in kidney cancer, PD-L1 was not predictive of response. However, in lung cancer and urothelial carcinoma, there seems to be more activity in higher expressing PD-L1 tumors.
I think that immunologists will be the first to tell us that we don’t really know what the appropriate assay is—whether we’re looking at tumor-infiltrating cells, stromal cells, etc. We don’t know whether or not these will change over time. The biomarker is as we describe it, based on how the trial was done, but how to use it going forward is unclear. There is a lot to learn.
Atezolizumab has been granted a priority review. What impact will an FDA approval have on the treatment landscape?
Given that bladder cancer is one of the last solid tumors that have a really amazingly unmet need, this will, overnight, change the management paradigm.