Steps Being Taken to Turn mRCC Into a Chronic Disease

Daniel M. Geynisman, MD

Personalized medicine for patients with metastatic renal cell carcinoma (mRCC) continues to be refined, as researchers are actively investigating therapeutic regimens that could change mRCC from a fatal disease into a chronic condition.

For example, an intriguing, ongoing phase I/II clinical trial is looking at the combination of the PD-1 inhibitor nivolumab (Opdivo) and the VEGF inhibitor axitinib (Inlyta) in patients with previously treated or treatment-naïve RCC (NCT03172754). Investigators are using overall response rate and incidence of treatment-related adverse events as the primary endpoints.

“There is hope and excitement in the field; there are a lot of options that we have, and there are options that are expanding,” said Daniel M. Geynisman, MD. “Over the last 10 years, if we look at outcomes, they have definitely improved—and they will continue to improve.”

OncLive: What did you discuss in your presentation on kidney cancer?

What does sequencing currently look like in this field?

What steps do you take with each patient to determine what sequence of drugs to use?

With a variety of agents available, what do you notice about patient preferences?

What ongoing clinical trials have the potential to change practice?

What does the future of this treatment landscape look like over next few years?

The kidney cancer field has seen great progress in recent years. What challenges remain?

Geynisman, an assistant professor in the Department of Hematology/Oncology, Fox Chase Cancer Center, lectured on the state of metastatic kidney cancer during the 2017 OncLive^® State of the Science Summit^TM on Renal Cell Carcinoma and Bladder Cancer. In an interview, he spoke on the remaining challenges in the landscape despite progress with systemic therapies and the pivotal ongoing studies combining immunotherapy and targeted therapy.Geynisman: I spoke about the current treatment landscape for metastatic kidney cancer and the various drugs that are approved now and are in the NCCN guidelines for that disease. It is a field that is rapidly changing and evolving, and I covered the last 10 years of treatment changes. Right now, as we speak today—although it may change tomorrow—we start with a tyrosine kinase inhibitor. Usually, there is sunitinib (Sutent) or pazopanib (Votrient) to start with and then we move on to drugs such as nivolumab, cabozantinib (Cabometyx), and lenvatinib (Lenvima)/everolimus (Afinitor). Those are the next 3 standard options. There are others available, but generally those are the 4 drug classes that we use. Every patient is unique and you have to really see what their needs are, what their comorbidities are, when you can make decisions about the drugs, what they can tolerate, and what their preferences are. Therefore, we are very fortunate now that we have a number of options—both intravenous (IV) and oral [formulations], immunotherapies, VEGF-targeted therapies, mTOR-targeted therapies, and combinations. This really depends on what the disease is like, what the patient is like, and what the best fit is for the patient. Not unexpectedly today, immunotherapy is very hot. That is usually one of the first questions that we are asked, and patients are very motivated and interested in participating in clinical trials of immunotherapy. That is one of the most important things that we talk about. It is also exciting for us because patients can derive tremendous benefit for a long time from immunotherapy, which is very different from most treatments that we have. There are a number of trials. Likely, the most exciting ones are the studies that combine immunotherapy with targeted therapy upfront for metastatic kidney cancer. Those trials are ongoing and the results will probably be out in the next 16 to 24 months; they will undoubtedly change the treatment landscape for this disease. Where it has been heading, and where it’s headed more and more is making metastatic kidney cancer into more of a chronic disease. That is what we would like to see happen and that is what is happening for a lot of our patients, but not all. As we get better at treating it, that is what we would like to do. We would like to personalize it more, figure out which patients we should use immunotherapy for upfront versus later, and that is where it is going to go. With any chronic disease, and especially oncology, treatments can be very expensive—both oral and IV treatments. Not necessarily for the patients but for us as a society, the medical profession, that is a big challenge that is actually getting worse. Therefore, we will have to figure out how to utilize our resources thoughtfully and appropriately, and that is something that we struggle with daily.