Combination Approaches for Metastatic Renal Cell Carcinoma - Episode 1

Historical Perspectives on the Treatment of mRCC


Nizar M. Tannir, MD, FACP: The treatment landscape of metastatic renal cell carcinoma has changed rapidly over the past several years. The advent of targeted therapies and immune checkpoint inhibitors has revolutionized the treatment of renal cell carcinoma.

There are several FDA approved agents that are on the market right now, starting with high-dose IL-2, which was approved in 1992. It took 13 years before we had the first targeted therapy, and that was sorafenib in December of 2005. A month later, sunitinib was FDA approved in January of 2006. In 2007, 3 therapies came to the clinic—everolimus, bevacizumab with interferon, and temsirolimus. So, 2 mTOR inhibitors and interferon with bevacizumab.

Then, in 2009, we had pazopanib, another TKI similar to sunitinib, and sorafenib. And then, in 2012, we had axitinib, another TKI directed against VEGF. In November of 2015, we had the first immune checkpoint inhibitor FDA approved for renal cell carcinoma. And then, in 2016, 2 therapies came to the market—cabozantinib, in April 2016, and a month later, in May 2016, it was everolimus plus lenvatinib.

Chung-Han Lee, MD, PhD: Historically, kidney cancer has been found to be resistant to both chemotherapy and radiotherapy. The big change has been the development of the targeted therapies. In this era of targeted agents, we have seen responses typically in the 9- to 12-month range for first-line TKIs, with objective responses somewhere within the 30% range and a clinical benefit rate somewhere around 60%.

Nizar M. Tannir, MD, FACP: When we talk about efficacy of therapy, we have to keep safety and tolerability in mind. The several therapies that we have just discussed for metastatic RCC present different challenges. These therapies have been FDA approved because of their efficacy compared with older therapies, such as cytokines or placebo.

The classes that we have discussed represent targeted therapies directed against the VEGF pathway, the mTOR pathway, and immune checkpoint inhibitors. It is important to keep in mind that each of these classes of agents requires knowledge of the mechanism of action, how to treat those patients, and how to manage adverse events.

Chung-Han Lee, MD, PhD: One of the big unmet needs in the field remains to be that there’s still no cure for people with metastatic kidney cancer. We have seen some long-term responses, but those continue to be few and far between. Approximately 20% of people do achieve what we would consider to be a long-term response to a first-line TKI, which would be either a complete response or a progression-free survival of approximately 18 months or greater. Right now, although these cures are not yet available, we are working very, very hard to enhance upon these historic gains.

Transcript Edited for Clarity