Brian Rini, MD, associate professor, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, discusses professional practice gaps and barriers to optimal care of renal cell carcinoma (RCC).

This analysis looked at the challenges associated with the delivery of care on the community level to patients with RCC. Rini says information is still needed regarding when to switch to a second agent, the optimal dosing of axitinib, and the choice of systemic therapy for poor-risk patients.

The data, both qualitative and quantitative, reinforces areas that need further investigation.

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Dr. Rini on  Barriers to Optimal Care of RCC

Brian Rini, MD, Associate Professor of Medicine, Department of Solid Tumor Oncology, Cleveland Clinic, discusses the oral targeted therapy axitinib (Inlyta), a targeted agent that selectively inhibits receptors 1,2, and 3 of the vascular endothelial growth factor (VEGF).

Axitinib is distinguished from other VEGF inhibitors by the AXIS 1032 trial comparing axitinib and sorafenib (Nexavar). The AXIS trial was the first trial to compare targeted therapies to each other in advanced renal cell carcinoma (RCC). Axitinib exhibited a 2-month increase in progression-free survival and more than a doubled objective response rate compared to sorafenib.

Trials comparing active agents provide the ability to compare relative advantages and disadvantages for efficacy and toxicity. It allows researchers to develop the correct sequences and determine which drugs may be better in certain circumstances.

Pfizer Inc filed a new drug application with the FDA in June seeking approval for the drug as a treatment for advanced RCC. On January 27, 2012 the FDA approved axitinib. 

FDA Approves Axitinib for Advanced Kidney Cancer Patients

Dr. Brian I. Rini from the Cleveland Clinic Discusses the VEGF Targeted Agent Axitinib 

Dr. Rini Discusses the VEGF Targeted Agent Axitinib 

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio, explains results from the AXIS 1032 phase III trial comparing axitinib to sorafenib in the second-line setting for metastatic renal cell carcinoma (mRCC). Retrospective data from the study indicated hypertension as a marker of superior outcome.

Dr. Brian I. Rini from the Taussig Cancer Institute Describes Hypertension as a Biomarker in RCC

Dr. Rini Describes Hypertension as a Biomarker

Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio, describes that there is a long ways to go in the progress of therapy for advanced RCC. He expresses that axitinib, a drug that he investigate in his AXIS 1032 phase III trial, represents the pinnacle of VEGF receptor therapy and he feels the VEGF inhibitor field may have reached the peak of its potency.

Dr. Rini says there is room for new drug development on the VEGF front as well as along other targets. Once axitinib is fully developed, it is likely that VEGF receptor inhibition will be maxed out and they will need to turn to other targets and other ways of giving the drug. Ideally, there will be better ways of selecting the patients who will have more response and less toxicity. Dr. Rini adds those points are investigational at present.

Dr. Brian Rini from Taussig Cancer Institute on the Progression of Advanced RCC Therapy

Dr. Rini on the Progression of Advanced RCC Therapy

Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio, discusses the lack of a current standard of care for advanced renal cell carcinoma. He describes how trials, such as the AXIS 1032 phase III trial comparing axitinib to sorafenib in the second-line setting for metastatic renal cell carcinoma (mRCC), can help improve treatment options for the disease.

Dr. Brian I. Rini from the Cleveland Clinic on Standards of Care for Advanced RCC

Dr. Rini on Standards of Care for Advanced RCC

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio discusses the integration of axitinib into the clinical practice, initially, he believes, in the refractory setting and soon in the front-line as new trial results come in, the most recent trial completed was the AXIS 1032 phase III trial comparing axitinib to sorafenib in the second-line setting for metastatic renal cell carcinoma (mRCC) which found axitinib to be superior to sorafenib.

Dr. Brian I. Rini from the Taussig Cancer Institute Explains the Axitinib Integration Process

Dr. Rini Explains the Axitinib Integration Process

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio looks at the 3 main categories of side effects found in the AXIS 1032 phase III trial comparing axitinib to sorafenib in the second-line setting for metastatic renal cell carcinoma (mRCC) which found that axitinib's side effects were more manageable and less bothersome than the sorafenib side effects.

Dr. Rini says the side effect profile generally fell into three categories and there were some that were more common with axitinib that were considered on target, VEGF inhibition effects. High blood pressure has been a classic response to the agents, especially the more potent agents. There was a group of side effects that appeared roughly equivalent between the arms. These included things like fatigue, diarrhea, and GI side effects. The three side effects that were more common in sorafenib patients were hand-foot syndrome, rash and alopecia. Dr. Rini says different patients will have different benefit and also different toxicities, which is part of the equation of approaching patients.

Dr. Brian I. Rini from the Taussig Cancer Institute Describes Axitinib's and Sorafenib's Side Effects

Dr. Rini Describes Axitinib's and Sorafenib's Side Effects

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio, explains the vascular enthothelial growth factor (VEGF) potency and comparison explored in the AXIS 1032 phase III trial comparing axitinib to sorafenib (both VEGF inhibitors) in the second-line setting for metastatic renal cell carcinoma (mRCC).

Dr. Rini says many doctors had a hypothesis that the agents that are more potent and selective against the VEGF receptor family, which is the major therapeutic receptor in kidney cancer, would produce clinical benefits. Up until now, there was no comparative data to support or refute that hypothesis. The AXIS 1032 phase III trial study, by in essence comparing a more potent versus a less potent VEGF inhibitor, provides data to say there is a clinical advantage to that biochemical drug advantage. Dr. Rini adds that other studies with other settings and other drugs are needed to flesh out the story, but the theme is becoming clearer as more clinical data is collected.

Dr. Brian Rini from Taussig Cancer Institute explains the Axitinib and Sorafenib AXIS Trial VEGF Potency Focus

Dr. Rini on the Axitinib and Sorafenib Trial VEGF Focus

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio discusses the axitinib and sorafenib AXIS 1032 phase III trial hazard ratio and explains why using the hazard ratio for the comparison of drugs is preferred to the median.

Dr. Rini says the median looks at one point in time on the curve while the hazard ratio looks at every point in time on the curve and how they relate to each other. With a hazard ratio of .6, it means that at any point in time the patient was about 30% to 40% less likely to progress if they were getting axitinib than if they were getting sorafenib. Dr. Rini says in those terms it is a different way of quantifying it as opposed to a median. He says the median is quoted more often because it's easier, but a hazard ratio is a much better interpretation of a relative drug effect.

Dr. Brian Rini from the Cleveland Clinic Taussig Cancer Institute on the Axitinib and Sorafenib Trial Hazard Ratio

Dr. Rini on the Axitinib and Sorafenib Trial Hazard Ratio

Lead investigator Brian I. Rini, MD, a staff member in the Department of Solid Tumor Oncology at the Taussig Cancer Institute at Cleveland Clinic in Ohio, explains the results of the AXIS 1032 phase III trial comparing axitinib to sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC).

Dr. Brian Rini from the Cleveland Clinic Taussig Cancer Institute on the Results From His Axitinib and Sorafenib Trial

Brian I. Rini, MD

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Dr. Rini on Barriers to Optimal Care of RCC