Arlene, O. Siefker-Radtke, MD
Immunotherapy agents may be taking the field of urothelial cancer by storm, according to Arlene O. Siefker-Radtke, MD, but the therapies are still only responding in 15% to 25% of patients.
“Clearly, immune checkpoint inhibition is here to stay,” says Siefker-Radtke, associate professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, clinical co-leader, Bladder SPORE Executive Committee. “We can stimulate the immune system and we are benefitting some of our patients who were previously incurable, yielding genuine durable partial and complete responses with these drugs. Unfortunately, the fraction is still low.”
Siefker-Radtke lectured on the dramatic shift in bladder cancer treatment during the 2017 OncLive®
State of the Science Summit on Genitourinary Malignancies. In an interview during the meeting, she shed light on the exciting advances in the bladder cancer field, why researchers should move past PD-L1 as a biomarker, and what combinations can be expected to move through the pipeline next.OncLive: Urothelial cancer treatment has drastically changed in less than 1 year. What did you highlight in your talk?Siefker-Radtke
: It truly is an exciting time to be in the field of urothelial cancer, since we’ve had our first approval for treatment in over 30 years. To finally have a new drug during my career is quite an exciting time. My presentation focused on the immune treatment and the immune landscape for the treatment of patients with urothelial cancers.
Many people don’t realize that urothelial cancer was the first tumor to have an associated immune response. We saw that with the development of Bacillus Calmette-Guerin (BCG) over 50 years ago, where they actually saw responses with urothelial tumors in patients getting BCG vaccinations. That is what led to the development of BCG as an intravesical therapy for treatment of urothelial cancer.
Over the years, we’ve tried to build on the immune response that we’ve seen in some patients. We even did a trial of interferon alpha given systemically with chemotherapy, which, while it worked and we saw activity, it was actually more toxic than MVAC chemotherapy. Again, this was a poor immune-modulating drug with interferon alpha given systemically.
However, more recently, PD-1/PD-L1 inhibitors are taking the field by storm. There are multiple companies, multiple drugs, and my current prediction is that all of them will be approved because they’re showing definite activity for urothelial tumors.
The first was atezolizumab (Tecentriq), which was approved on May 18, 2016. For those in the field, [that date] is the equivalent of knowing where you were when Lady Diana passed away or when the Twin Towers fell. For me, it’s knowing when the first drug was approved. It was atezolizumab in the second-line treatment of patients who received prior cisplatin-based chemotherapy. Response rates were on the order of 15% with a median survival of 10 months. What is truly exciting about these drugs is the durability of responses that we are seeing with them.
We are seeing this with other drugs, as well. The PD-1 inhibitor nivolumab (Opdivo) was recently approved for a similar setting—cisplatin-failures and second-line treatment of urothelial cancer. Response rates appear similar; you could argue that the 20% to 25% is better than 15%. Patient selection can certainly be contributing to that. The median survival is again very similar to what we saw with the atezolizumab data.
What all of these drugs are showing are durable responses. I personally have patients on immune-checkpoint inhibitors who have been on therapy with durable partial, and even complete, remissions now for over 2 and a half years.
When we see the durable long-term benefit in these patients, it does leave one to wonder: are we going to see a cure with checkpoint inhibitors? It is too early to tell. We see a measure of 5 years in most cases. We are seeing this durable benefit that’s giving everyone hope that we’re going to cure a previously incurable group of patients with bladder cancer. In your lecture, you suggested it’s time we throw PD-L1 as a biomarker by the wayside. Why?
PD-L1 hasn’t been a good marker for patients with urothelial cancer. There have been hints in some studies that the response rate might be improved when you look at the PD-L1 expression on the immune infiltrate in addition to PD-L1 expression on the tumor cell.