Jorge Garcia, MD
With 5 checkpoint inhibitors approved for the second-line setting of urothelial carcinoma treatment, and 1 available for a frontline indication, how will researchers choose which drug to administer to patients?
The answer to that question remains in flux, explains Jorge Garcia, MD, because if pembrolizumab (Keytruda) is given as a frontline therapy and a patient’s disease progresses, it makes little sense to immediately administer another PD-1/PD-L1 inhibitor. The other newly approved PD-1/PD-L1 therapies include nivolumab (Opdivo), atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi).
Researchers are aiming to answer these questions and also improve patient outcomes with other options, such as combination regimens, in a number of ongoing trials. One such combination is pembrolizumab plus chemotherapy—a regimen that was recently approved by the FDA for the frontline treatment of patients with non–small cell lung cancer.
In an interview during the 2017 OncLive®
State of the Science SummitTM
on Genitourinary Cancers, Garcia, a medical oncologist at Cleveland Clinic, discussed how the field of bladder cancer has transformed with the FDA approval of pembrolizumab, and how oncologists should choose between 5 checkpoint inhibitors now available for the second-line setting and beyond.
OncLive: Can you provide an overview of your lecture on bladder cancer?
We discussed the standard of care that has existed in bladder cancer for the last 20 years or so. Then, I dove into immunotherapy and the emerging role of PD-1 inhibitors. Now, we have 5 agents that are FDA approved as of today. I briefly reviewed the data of each of those trials and put that data into context when you look for biomarkers and patient selection: What does the future hold for bladder cancer?
Pembrolizumab was recently granted approval by the FDA. What impact is this decision going to have?
That is a huge and important approval for us because, thus far, the approval and the registration of atezolizumab, avelumab, nivolumab, and durvalumab have all been in the context of phase I/II studies that are based upon response rates and durability of responses. However, none of the trials has had survival benefit. Pembrolizumab and the KEYNOTE-045 trial demonstrated, for the first time, that a checkpoint inhibitor in the second-line space against chemotherapy was able to lead to a survival benefit in patients in that context.
First, it is the only agent with survival data. Secondly, it indeed can be utilized in the frontline setting for patients with platinum-resistant disease to some extent. That will be the newer standard of care for patients in that context.
Now, how do you put that data into context with the IMvigor data from Genentech/Roche, that was in a press release, as a negative trial? It randomized patients to atezolizumab versus chemotherapy. That trial’s press release was negative for survival. We have to wait to see the data to put it into context.
It has been more than 1 year now since the first checkpoint inhibitor was approved. What has it been like for you to see this invasion of immunotherapy unfold?
It has been great, because bladder cancer has been traditionally considered an orphan disease. There fully have not been any data supporting any treatment for the last 10 to 15 years outside of chemotherapy. That is rewarding for us and for our patients; it allows them to have options. The tricky part of getting 4 to 5 agents approved within 24 months is, which one are you going to use? Do we need to use all 5 treatments when roughly, biologically, they may be the same?
Most people will get 1 of them and then we will move on [to something else]. The biggest challenge for us in the field is what to do after you get a checkpoint inhibitor. Most patients who receive checkpoint inhibition won’t derive any benefit from immunotherapy. The people who really want to be on a PD-1 inhibitor are the ones we want to pick from the get-go—they are likely to respond, likely to have a durable response, and maybe possibly be cured.
But, the vast majority of patients do not have a benefit. The biggest question right now resides in biomarkers. Can we detect, or utilize a test, to tell us that patients should or should not be on a checkpoint inhibitor?