We are getting a glimpse that perhaps when you combine several aspects of the tumor into a model, that you could better predict who can receive single-agent therapy. It is not only important to bring the treatment into the frontline setting, but now we are going to the adjuvant setting. There, it is even more important that the right patients are getting the right treatment because most of those patients are already cured by surgery. Hopefully, we can extend what we are learning in the metastatic setting into earlier disease to identify the patients who should get this treatment.
What is the outlook on immunotherapy as a standard of care in RCC?
Immunotherapy is already a standard of care for those who fail on a VEGF TKI. With CheckMate-214, it almost certainly will be FDA approved in the frontline setting. Whether that indication will be for the intermediate- and poor-risk groups or for the all comers, we must wait and see—but it will be standard of care in 2018, no doubt.
Even if it is standard of care, it still won't benefit every patient, and there are some patients who may get more benefit with VEGF strategies. That is one other aspect that came out of CheckMate-214: patients with good-risk clinical features did very well with sunitinib. Therefore, there may be some patients who can start on single-agent VEGF inhibitor, others that could start with single agent PD-1 blockade, and others who might benefit from the combination. Hopefully, that is the future that we are going to see, but we are not there yet.
Are there any novel agents or combinations that are looking particularly interesting?
The next big thing in kidney cancer is the combination of VEGF blockade and PD-1/PD-L1 blockade. There are probably 5 or 6 large randomized trials looking at various combinations. The early data from phase I trials, which are admittedly small sample sizes while patient selection is interesting, show that there are high response rates and longer PFS than you'd expect with either strategy alone.
Hopefully, as we get into 2018 and 2019, we will start seeing the results of these randomized trials. If they are positive, we could see the fusion of the 2 effective strategies for kidney cancer in the first-line setting. Perhaps there will be 5 or 6 versions of combinations, which will make things messy—so we will have to sort it out—but that'll probably be the next big thing for metastatic patients.
What should clinicians understand about immunotherapy in RCC?
First, immunotherapy is important. However, it should be rationally applied to patients who are most likely going to benefit. There are patients who get a tremendous benefit, and there are others who get none. We should identify those patients, and probably not be treating every patient [with immunotherapy]. That goes for both bladder and kidney cancer. While there are some patients who need combinations, single agents still do work for some patients and we should stick with those and look at proper sequencing. Some patients are going to need more than one strategy. However, it is an exciting time with a lot of new data.
Is there anything else that you would like to add?
There are a series of adjuvant immunotherapy trials that are up and enrolling. If you have a patient who has just had surgery and is interested in immunotherapy, there are at least 2 trials open; one is with atezolizumab (Tecentriq) and one is with pembrolizumab (Keytruda).
As for options before surgery, there is a very interesting trial looking at nivolumab before surgery and then after surgery. Therefore, there are choices for patients with stage III disease and, hopefully, people will be open to those trials and consider their patients for them.