Recent Advances in RCC Treatment

EP: 1.Overview of Renal Cell Carcinoma (RCC)

EP: 2.Classification of Renal Cell Carcinoma

EP: 3.Approaching Treatment for RCC

EP: 4.Goals of Therapy for RCC

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EP: 5.Recent Advances in RCC Treatment

EP: 6.Phase 3 CLEAR Trial in mRCC

EP: 7.Emerging Agents for the Treatment of RCC

EP: 8.Treatment Selection for the Management of RCC

EP: 9.Managing Adverse Events in RCC

EP: 10.Role of Combination Therapy in RCC Management

Thomas E. Hutson, DO, PharmD: Since 2005-2006, we now have several other vascular endothelial growth factor [VEGF] inhibitors that have been approved. We have a couple new types of drugs. One of them is called a mechanistic target of rapamycin [mTOR] inhibitor, the other is now called a checkpoint inhibitor, or an immune therapy. Thus, together with the VEGF inhibitors we have three broad classes of drugs to choose from: VEGF inhibitors, mTOR inhibitors and checkpoint inhibitors or immune therapies. The VEGF inhibitors, as I mentioned, work by blocking that VEGF factor. The mTOR inhibitors block the mTOR pathway, which is another important cancer pathway. The checkpoint inhibitors, which have been the newest development, is really an area we could spend a lot of time on. The discovery of checkpoint inhibitors actually resulted in the winning of a Nobel Prize for medicine a couple years ago by one of the physicians at [The University of Texas] MD Anderson [Cancer Center], and a movie was made about it. Checkpoint inhibitors have shown to be of benefit not just for kidney cancer, but roughly half of all cancers.

A checkpoint inhibitor is an antibody. It's something that is made that is an antibody that is given to a patient, which goes in and actually turns on the immune system of the patient. Even though it's an infusion, don't be concerned that it's a poison or it's a toxin, or it's like any other chemotherapy. This is just an antibody therapy, and it goes in and it turns on your immune system, and the actual anti-cancer effect is from your own body's immune system turning on and fighting the cancer. Again, this works in about half of all tumors. Why it works has been something that we've been long wondering about in kidney cancer. We have shown for decades that for some reason the immune system did not respond to the kidney tumor. When the kidney tumor was removed and looked at under the microscope, we could see white blood cells, which normally fight infection in cancer, were sitting next to the tumor and they were not doing anything.

Now, we have discovered with this checkpoint inhibitor why that is. It's because the cancer was essentially turning off the immune system, and how it was doing it are through cells, which touch each other and talk to each other, and as the cancer cell would bump into the immune cell it would just shut it off. Thus, this checkpoint, this antibody was designed to go in there and prevent that, so it prevents that turning off of the immune system, allowing your own body then to recognize the cancer, develop an immune response, and in many patients that results in shrinkage of tumor and in rare situation, 10% or so in kidney cancer, tumors can go away.

These therapies are new for kidney cancer; they were developed in 2015 and 2016 and were approved for kidney cancer about that time, and so we're now just gaining experience with them. Also, we have recently reported that patients that get these checkpoint inhibitors have near complete responses and can go off of all therapy, and that that response is durable for now at least up to four years. Again, it's been a significant advance in the management not only of kidney cancer but other cancer types. In summary, there are 3 broad categories of therapies for kidney cancer. VEGF inhibitors, which are oral therapies; mTOR inhibitors; and then checkpoint or immune therapies which are antibody IV therapies.

This transcript has been edited for clarity.