Sandy Liu, MD: If I start a patient on a first-line targeted agent, there are just 2 reasons why I would stop a first-line treatment or why it would be unsuccessful. First is if they’re really not able to tolerate the medication. If the side effects, despite aggressive management — dose withholding and dose reduction — are not able to be tolerated, I would stop the therapy and deem it unsuccessful. The second reason why I would stop therapy in the first-line setting is because of progression of disease. When I start a therapy, I will typically repeat imaging every 3 months to monitor their response to treatment. If I see that the tumor is getting bigger or if there are new tumors popping up, then I would deem it unsuccessful and change to a second-line therapy. There are many options for second-line therapy.
Options for second-line therapy for patients who progress during first-line therapy or can’t tolerate first-line therapy would be another targeted agent. There are several. There are about 6 or 7 targeted agents approved for kidney cancer. I would move on to the next targeted agent. If they had Votrient (pazopanib), I would use Sutent (sunitinib). Cabozantinib would be another great second-line drug. Nivolumab, which has a completely different mechanism from the targeted agent—it’s an infusion immunotherapy through IV—is another good option as second-line treatment. Another class of agents is the mTOR (mechanistic target of rapamycin) inhibitors. There’s temsirolimus, which is an IV agent, and everolimus, which is an oral agent. That is a potential option. However, in the second- and third-line setting, I definitely do consider patients for a clinical trial whenever possible.
Quality of life factors most importantly in my decision making when I recommend a treatment option, because these treatments are not benign. They do have side effects. If I see a patient and I know that they’re going to struggle with a medication and it’s going to be a class effect—and the side effects are generally the same—I tend to go to another class like immunotherapy in the first or second-line setting. Generally, immunotherapies do have their own side effects, but the side effects are different from the targeted agents. They’re much more tolerable. I have given immunotherapy to 80- or 90-year-olds, and they do pretty well. If the side effect profile really interferes with their quality of life, I generally tend to take that into consideration and recommend an alternative therapy.
There are other factors that I consider. We haven’t talked about different types of kidney cancers. The most common type is clear cell, which makes up about 75% to 80%. There are non-clear cell renal cell carcinomas that don’t have a good, clear standard of care, and we treat them as clear cell disease because there are really not a lot of good options. So, if I see a patient who has non-clear cell disease like papillary or chromophobe or collecting duct carcinoma, I treat them completely differently sometimes. I definitely consider them for a clinical trial, but if they don’t have any other options, I basically treat them like a patient with clear cell disease.