First-Line Kidney Cancer Treatment: Targeted Therapy
Sandy Liu, MD: Right now, the current standard of care for first-line treatment is still targeted therapy. Targeted therapy was first approved by the FDA (Food and Drug Administration) in about 2005 with sorafenib, followed by sunitinib in 2006. Targeted therapy specifically targets angiogenesis, and angiogenesis is blood vessel formation. Blood vessels go to the kidney cancer to grow and proliferate, and we want to block the blood vessel formation that goes to the kidney. Right now, there are several targeted agents approved in the first-line setting. Sunitinib (Sutent) is one of them, Votrient (pazopanib) is another, and most recently approved in December of 2017 is cabozantinib. Cabozantinib was compared head-to-head with sunitinib, and it actually outperformed sunitinib. So now, I typically prescribe cabozantinib to my patients in the first-line setting. Cabozantinib is a good targeted agent because it has three pathways. It targets the VEGF pathway, which is responsible for angiogenesis. It also targeted MET and AXL. VEGF, MET and AXL are 3 key receptors that play a role in cell growth, cell death and cell progression in cancer.
When I do recommend starting targeted agents for my patients in the first-line setting, I go over the side effects, I go over the dosing, and I go over how to manage side effects. First, I go over the side effects, and it’s really a class effect of these targeted agents. The most common is fatigue. That’s the most common, and they also cause high blood pressure and hypertension. They cause thyroid dysfunction. They interfere with wound healing and bleeding. They can cause a rash. They can sometimes cause mouth sores or hair color changes. We need to monitor their blood tests, especially their blood counts, kidney function and liver function. We have to monitor their urine, because sometimes they can leak a little bit of protein in their urine. I go over all these effects, and I tell them that these side effects can all be managed as long as they know what to look for and they tell me, so we can manage it.
I like to see patients very frequently the first time I start them on any of the oral agents, sometimes every 2 weeks in the beginning, and then I spread it out to every month or sometimes every 6 months. I make sure that their blood pressure is well-controlled before I start any oral targeted agents and make sure that there’s nothing that causes wound healing or blood clotting before I start. If I do start, I start at the regular doses. If they have any side effects, what I tend to do depends on the side effect. If it’s fatigue that can be managed with exercise, I tell them exercise is the best way to combat fatigue. If despite exercising they still have a lot of fatigue, I tend to hold the medication and then restart it at a lower dose.
Holding the dose and restarting at a lower dose is typically what I do. If there’s any hypertension, I start an antihypertensive. If there’s any thyroid dysfunction, I start a thyroid hormone replacement. Rash can be easily handled with moisturizers and urea cream. Mucositis or mouth sores can be handled with mouthwashes. All of these side effects are definitely manageable. Patients just have to know what to look for and to tell their physician, and they can be managed with dose reduction and dose withholding.
Cabozantinib was recently approved in the first-line setting. It was originally approved in 2016 in the second-line setting and beyond. Cabozantinib is a great option in the first-line, second-line and beyond settings. In a patient with newly diagnosed stage 4 advanced disease, if they don’t have any contraindications to cabozantinib, it’s certainly one of the drugs that I do discuss with patients, because it’s a great medication. It’s very effective. It was compared with Sutent head-to-head, and it actually outperforms sunitinib. I would definitely discuss it with all my patients. If they had a different oral targeted agent in the first-line setting, like Sutent or Votrient, I would discuss cabozantinib in the second-line setting.
My personal clinical experience with cabozantinib has been pretty good. I have started several patients on cabozantinib, and they’ve been doing extremely well now. The side effects are predictable, and my patients know what to watch out for. The main thing that I am dealing with is hypertension with cabozantinib, which has all been managed. I do have patients who have some thyroid dysfunction, which I have thyroid hormone replacement for. There have been rashes and mouth sores, which are all managed with mouthwashes and moisturizers. My personal experience has been very good with cabozantinib, and patients are able to tolerate it with dose reductions.