Immune Checkpoint Inhibition in Renal Cell Carcinoma

Panelists: Robert A. Figlin, MD, Cedars-Sinai; Daniel J. George, MD, Duke; Thomas E. Hutson, DO, PharmD,
Texas Oncology; Eric Jonasch, MD, MD Anderson; Brian I. Rini, MD, Cleveland Clinic
Published Online: Wednesday, September 18, 2013
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Traditionally, immunotherapeutics have played an important role in the treatment of renal cell carcinoma (RCC), explains moderator Daniel J. George, MD. At one point, the cytokine therapy interleuken-2 (IL-2) was a common first-line therapy for patients with RCC but, as a result of higher responses in more patients with fewer severe side effects, IL-2 was eventually replaced by VEGF targeted agents in the first-line setting.

The discovery of more sophisticated immunotherapies, such as nivolumab, may result in this class of agents regaining its previous role in the treatment of RCC, believes Brian I. Rini, MD. Nivolumab blocks the PD-1 receptor, placing it in a class of agents known as checkpoint inhibitors. In the immune system, checkpoints operate as brakes to slow down or stop immune response, including anti-tumor immune response. Inhibiting immune checkpoints effectively takes the brakes off the immune system allowing for anti-tumor activity, suggests Rini.

The efficacy and safety of nivolumab was explored in a large phase I trial that enrolled patients with a variety of tumor types, including 34 patients with advanced RCC. In this study, the overall response rate (ORR) by RECIST criteria was 29% for patients with RCC, demonstrating a clear anti-tumor activity with nivolumab as a single-agent, states Rini. As demonstrated by this trial, the percent of patients who benefit from nivolumab is much higher than previous immunotherapies in RCC that only elicited durable responses in 5% to 10% of patients.

As a result of this high response rate, nivolumab is being developed extensively in kidney cancer as a single-agent and in combinations, specifically with the CTLA-4 inhibitor ipilimumab, Rini says. A phase III registration trial is currently in progress comparing nivolumab to everolimus for patients with advanced RCC previously treated with antiangiogenic therapy. The primary endpoint of this trial is overall survival (OS), with progression-free survival and ORR as secondary endpoints. Moreover, Rini notes, the trial is also assessing OS specifically in PD ligand 1 (PD-L1) positive and negative subgroups, as a potential biomarker of response.

Determining the best point in the sequence to utilize checkpoint inhibitors seems to be the next big question, believes Eric Jonasch, MD. The ideal setting for these agents may overlap with areas where antiangiogenic TKIs have traditionally been used. However, this may be warranted, since the profound benefit with checkpoint inhibition could ultimately result in a fraction of patients being cured, states Jonasch. As a result of the long-term durable remissions seen with checkpoint inhibitors, there may be a need to change the design of clinical trials to include more appropriate primary endpoints, Robert A. Figlin, MD, believes.

View More From This Discussion
Episode 1 Introduction and Review of the COMPARZ Trial in RCC
Episode 2 COMPARZ Trial and Alternate Sunitinib Dosing Schedule
Episode 3 PISCES Trial and Patient Treatment Preference in mRCC
Episode 4 AGILE Trial: Frontline Axitinib Versus Sorafenib in mRCC
Episode 5 Utilizing Frontline Bevacizumab in mRCC
Episode 6 Frontline Sunitinib Compared to Everolimus in mRCC
Episode 7 AXIS Trial: Second-Line Axitinib Versus Sorafenib
Episode 8 Determining Progression in Renal Cell Carcinoma
Episode 9 INTORSECT Trial: Second-Line Temsirolimus Versus Sorafenib
Episode 10 Novel Agents in Development for Renal Cell Carcinoma
Episode 11 Immune Checkpoint Inhibition in Renal Cell Carcinoma
Episode 12 Unmet Needs in Renal Cell Carcinoma
Episode 13 Conclusion: Key Take-Away Points and Cardiac Safety
Expert Panelists
Dr Daniel George

Daniel J. George, MD

Director of Genitourinary Oncology
Duke Cancer Institute
Durham, North Carolina

Robert A. Figlin, MD

Professor of Medicine and Biomedical Sciences; Chief, Division of Hematology/Oncology
Cedars-Sinai Comprehensive Cancer Center
Los Angeles, California

Thomas E. Hutson, DO, PharmD

Director of Genitourinary Oncology, Texas Oncology; Professor Medicine, Texas A&M
Health Science Center, Dallas, Texas

Eric Jonasch, MD

Associate Professor of Medicine
University of Texas MD Anderson Cancer Center, Houston, Texas

Brian I. Rini, MD

Professor of Medicine, The Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio
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