Future Strategies in Kidney Cancer Treatment - Episode 2
James J. Hsieh, MD, PhD: Cancer is a very complicated disease, especially kidney cancer. So, everybody needs to be engaged and everybody needs to be involved before we can provide the best care for our patients. When a patient is presented with symptoms, they normally go to get a study like a CT scan done. The radiologist needs to make a call, and they will send the patient—if they found a kidney mass—to see the urologist to cut it out. When they cut it out, the pathologist needs to evaluate it to see what kind of kidney cancer this patient actually has. If this patient developed metastatic disease, he’ll be taken care of by a medical oncologist and a radiation oncologist. So, there are so many people involved. It’s a multidisciplinary approach.
If the patient gets systemic treatment, they’ll have toxicity. There, you need to have a specialist to deal with it—especially dermatologists, who we work with closely, because the last of the VEGF drugs caused a lot of skin toxicities. It’s a multidisciplinary approach. I think to move this field even further we need to engage scientists—physician scientists, like me. What we can actually do is try to understand what’s really going on in the disease, and then we can move the disease forward. We form a multidisciplinary team, that way.
Thomas Hutson, DO, PharmD, FACP: Overall, survival and quality of life have improved dramatically over the past decade for patients with metastatic renal cell carcinoma. The biggest incremental gains were during the approvals of the first-in-class agents, sorafenib and sunitinib. When they were compared to interferon, we saw more than a doubling in progression-free survival, and what we believed to be a real doubling of overall survival. Since then, with the approval of several other agents—many of them in the same class—we have inched up overall survival even further. At the same time, with the development of more targeted agents, we’ve been able to ameliorate some of the toxicity concerns, which has allowed an improved quality of life for patients with this disease.
Now, with 9 available therapies for use in the United States, we will use those sequentially and patients can hope to get 3 to 5 times longer overall survival than what they could of when we were back in the cytokine era using agents like interferon. To put it another way, many of our patients can expect to live 4 to 5 years, or longer, with our current available therapies, and enjoy a reasonable quality of life that will allow many of them to continue to work in the occupations that they had prior to their diagnoses.
Our initial approach to the treatment of metastatic renal cell carcinoma has evolved and changed over the years as new agents have become available and have entered into our group of agents that we can choose from. However, unfortunately, our first-line agents—sunitinib and pazopanib—have remained the staple of care for the past 4 to 5 years. I am here to report—and we’re seeing this now at major meetings, such as the ESMO Congress and this year’s 2017 ASCO Annual Meeting—that combination therapies are here to stay. We may actually see, as phase III trials are undertaken and mature, that we will now supplant our single-agent frontline therapies with combination strategies.
So, the first-line setting has been stable, but we expect changes as we move forward with combination strategies. In the second-line setting and beyond, we’ve seen significant shifts. Our newest agents—there have been 3 in the past year: nivolumab, the combination of lenvatinib and everolimus, and cabozantinib—have pushed the bar in the second-line and refractory setting and have supplanted the previous use of other agents in that space.
The bar has been set high with these agents, and in order to push survival and quality of life even further, we need to start looking at innovative ways of administering the medications, looking for potential new targets, and exploiting potential combinations. Combination strategies in cancer therapy are not a new concept. We, as cancer doctors and pharmacologists, have wanted to combine agents with different mechanisms of action. Now, for the first time in kidney cancer, we have several classes of agents with different mechanisms of action that don’t have, necessarily, overlapping, dose-limiting toxicities. Therefore, if we’re able to combine these agents with different mechanisms of action and different dose-limiting toxicities, we may be able to push up the efficacy bar without compromising quality of life and toxicity endpoints. So, strategies that are being employed now—and we saw this at the 2017 ASCO Annual Meeting—are combining the proven VEGF-targeted therapies, which are the current standard of care for the disease with the newer agents, such as the immune oncology drugs.
Transcript Edited for Clarity