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Future promising for renal cell carcinoma management
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The 21st century has witnessed several practice-changing advances in managing patients with renal cell carcinoma, including a steadily growing armamentarium that has resulted in improved patient outlook. In an interview with Healio, Brian I. Rini, MD, professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and staff member at the Cleveland Clinic’s Taussig Cancer Institute, shared his thoughts on these changes and what drives him in research, and offered a glimpse at what he believes the future of renal cell carcinoma treatment will entail.
What was the motivating factor that led you to pursue renal cell carcinoma as a primary research interest, and how has the field sustained your interest?
I have been actively involved in renal cell carcinoma research for more than 15 years. When I started, not many therapeutic options were available; in fact, there was only one FDA-approved drug. So, the motivation was to find more options to help patients. And during the last decade or so, that is exactly what has happened — first with targeted therapy and currently with immunotherapies, as there are now 11 FDA-approved drugs. These advances in the field have more than sustained my interest.
How has your view of renal cell carcinoma changed since you first began your career?
My outlook has become much more optimistic. Since I was in late fellowship and early faculty, the median survival has roughly tripled from about 1 year to now more than 3 years. With the emergence of novel therapies, patients can now receive two, three or four therapies, which has helped extend survival.
In recent years, research into renal cell carcinoma has experienced both highs and lows, from breakthroughs in immunotherapies to the continuing struggle to find a suitable biomarker. What are your thoughts on the state of clinical research today?
A lot of promising immunotherapies are being tested at the moment, with combinations now in phase 3 testing. In my practice, for instance, we are heavily invested in immunotherapies, so a lot of our time, resources and patients are going to the trials testing combination therapies. Specifically, we are examining different ways to administer the combinations, different strategies in clinical practice and toxicity management. Other novel targets, such as inhibitors of LAG-3, TIM-3 and IDO, are promising but are in relatively early development. Overall, there are hundreds of different ways to manipulate the immune system, and various ways of doing so should play out over the next few years.
In terms of finding a viable biomarker in kidney cancer, it has certainly been a challenge. I am not sure why this has been the case, but it is a challenge in many diseases, not just renal cell carcinoma. Expression of PD-L1 on tumor and/or immune cells has been extensively studied. Although promising initially, most data sets have not supported its use. Recent data from the phase 3 CheckMate-214 trial testing the combination therapy of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) in renal cell carcinoma, however, suggest an association of expression with response. More data are needed to know if this is important in clinical practice.
During the past year, what have been some of the most eye-catching trials in the field of renal cell carcinoma?
At the 2017 European Society for Medical Oncology Congress, investigators presented data from the aforementioned CheckMate-214 trial, with publication expected soon. According to the presentation, the combination of nivolumab and ipilimumab improved the objective response rate and prolonged overall survival among intermediate- and poor-risk patients with advanced or metastatic renal cell carcinoma when compared with sunitinib (Sutent, Pfizer).1
Additionally, the phase 3 IMmotion151 trial, which was recently presented at the 2018 Genitourinary Cancers Symposium, tested a different combination — atezolizumab (Tecentriq, Genentech) plus bevacizumab (Avastin, Genetech) — compared with sunitinib. The trial indicated that the combination therapy significantly reduced the risk for disease progression in patients with advanced or metastatic renal cell carcinoma compared with sunitinib.
Both of these data sets show that immune-based combinations are likely to be the standard of care for untreated metastatic renal cell carcinoma in the near future. More data on other combination therapies in phase 3 testing are sure to follow as well.
How do you predict the treatment of renal cell carcinoma will evolve in the future?
We will very quickly move to combination therapy up front involving an immune-oncology agent. Afterward, we will return to giving targeted therapy to most patients, which will dominate the landscape for a while. Beyond that, it is hard to know exactly what the next steps will be. I anticipate that during the next couple years we will sort out the best combinations and determine which patients might be suitable for which combination.
Ultimately, the way we approach this disease is going to change dramatically over the next 1 to 2 years as these combinations come out. Right now, we just give one targeted therapy to patients as initial therapy; this is going to change in that everyone will receive combinations that include an immune-oncology agent.
What advice would you offer a student whose goal is to treat patients with renal cell carcinoma?
I would say, regardless of your specialty of medicine, you should find a niche or an area of the disease that you are interested in, pursue it and develop an expertise in that field. In kidney cancer, being an expert in immunotherapy management and treatment of adverse effects is extremely helpful. However, this is not exclusive to kidney cancer and is true of many diseases.
References:
Escudier B, Tannir N, McDermott DF, et al. CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Presented at: European Society of Medical Oncology Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA5.
Motzer RJ, Powles T, Atkins MB, et al. IMmotion151: A randomized phase III study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC). Presented at: Genitourinary Cancers Symposium; February 8-10, 2018; San Francisco, California. Abstract 578.
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