Jonathan E. Rosenberg, MD
The PD-1/PD-L1 inhibitors moving through the pipeline in bladder cancer will have a lasting impact on the armamentarium in the field, explains Jonathan E. Rosenberg, MD.
The impact of immunotherapy began with the May 2016 accelerated approval of the PD-L1 inhibitor atezolizumab (Tecentriq), based on phase II results of the IMvigor 210 study that showed an overall response rate (ORR) of 14.8% with atezolizumab.1
Next, nivolumab (Opdivo) was granted a priority review designation by the FDA in October 2016 as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-containing therapy. The decision is based on findings from the phase II CheckMate-275 trial, which showed an ORR of 19.6% in patients treated with nivolumab.2
Finally, at the recent 2016 SITC Annual Meeting, findings were presented from the KEYNOTE-045 trial, which demonstrated a 27% reduction in the risk of progression or death with pembrolizumab (Keytruda) versus chemotherapy in patients with advanced urothelial carcinoma whose disease progressed after prior treatment.3
Rosenberg, a medical oncologist at Memorial Sloan Kettering Cancer Center, lectured on the advancements with immunotherapy in bladder cancer during the 2016 OncLive
State of the Science Summit on Genitourinary Cancers.
In an interview with OncLive
, he discussed nivolumab, pembrolizumab and other emerging immunotherapies in bladder cancer, and how oncologists will tackle sequencing challenges should multiple agents become available.
OncLive: What were some of the highlights of your discussion on immunotherapy in bladder cancer?
: We have seen a tremendous explosion in potential new treatments for bladder cancer over the last 2 years. We have multiple new drugs that are in advanced phase clinical trials and a new drug approved in the United States—atezolizumab—that is the first PD-L1 inhibitor to actually be approved. We are expecting, over the next year, 2 to 3 approvals for similar types of agents.
Recently, at the 2016 SITC Annual Meeting, there were data presented on pembrolizumab versus chemotherapy and it is said to be a positive study favoring pembrolizumab.
We have also seen recent data with nivolumab that is showing substantial activity in a large phase II study that was presented at the 2016 ESMO Congress. Between these 2 other agents, as well as drugs such as the PD-L1 inhibitors avelumab and durvalumab, we have a staple of really exciting new drugs that are being tested in this disease.
This must be very exciting for the field. What are your thoughts on how the treatment paradigm is evolving?
It’s a sea change in bladder cancer treatment. We are seeing efforts now to look at it instead of chemotherapy in some patients. There are 2 clinical trials that have shown that patients who cannot get standard cisplatin—because of other health issues in terms of nerve damage, kidney function, or just overall status—that we actually see these drugs being quite active and survival seems to be just as good, if not better, in randomized trials. We don’t know for sure yet.
The current indication for atezolizumab is only in postchemotherapy, but the data are promising in showing that people live as long with atezolizumab as they would if they got cisplatin in patients who can’t get cisplatin. While that’s not perfect data, it is certainly a very encouraging first step.
As time goes on, we are going to see this possibly replace chemotherapy or push it back to a situation where, if immunotherapy fails, then they get chemotherapy. It is a lot of investigation going on; we are even looking at it earlier in preoperative therapy to see whether or not we can stimulate an immune response that may have long-lasting effects.
Additionally, there are postoperative trials going on for patients who have high-risk disease. Those trials are accruing patients who have received chemotherapy before surgery and the cancer is still aggressive, as well as patients who have disease that is high risk and cannot get chemotherapy. Those are randomized trials that are accruing globally.
Do these immunotherapy agents have the potential to move into frontline?
For some patients, it is clearly going to be a first-choice therapy. We need to explore whether or not there are benefits to combining immunotherapy and chemotherapy. In a lot of diseases, it hasn’t been beneficial. However, in bladder cancer, we have chemotherapy that does actually work quite well for patients. There may be some synergistic effects and we need to explore that in multiple clinical trials.