Daniel J. George, MD, is the Eleanor Easley Distinguished Professor, a professor of medicine, a professor in urology, and a professor in surgery at the Duke University School of Medicine and a member of the Duke Cancer Institute.

Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses results of the Abi Race study for patients with metastatic castration-resistant prostate cancer (mCRPC).

Abi Race was a prospective, multicenter study of Caucasian and African-American patients with mCRPC treated with abiraterone acetate (Zytiga) and prednisone. Data presented at the 2018 ASCO Annual Meeting suggested that African-American patients responded better to the treatment. African-American men had higher rates of hypertension and hypokalemia, which George says is a direct result of abiraterone acetate lowering the adrenal gland’s functionality. Researchers hypothesize that in African-American patients, their tissue is getting greater exposure to abiraterone.

George adds that these results send a clear message that race-based trials are justified. Patients will accrue to these studies, and it’s likely to see differences in clinical efficacy and adverse events. It’s not the skin color that’s important, it’s the genes associated with skin color that can affect treatment response.

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Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses results of the Abi Race study for patients with metastatic castration-resistant prostate cancer.

Dr. George on Results of the Abi Race Study for Prostate Cancer

Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses an analysis of the S-TRAC study in renal cell carcinoma (RCC).

S-TRAC was a phase III, prospective, multicenter study looking at the effectiveness of sunitinib (Sutent) versus placebo in patients with RCC who were at high risk for disease recurrence—particularly patients with T3 or node-positive disease. George says that in a prospective study, treatment with sunitinib up to 1 year was found to delay disease-free survival by about 24%.

In an analysis of higher-risk patients with T3 or higher-grade disease, node-positive T4 disease, or a decreased performance status of 1 or less, investigators saw a greater overall benefit associated with 1 year of sunitinib. There was a 27% reduction in the risk of disease recurrence, which was a sustained benefit up to 5 years, George reports. He adds that as patients at a greater risk of recurrence are enriched, the benefit of sunitinib increases. This reinforces that high-risk patients benefit from sunitinib, especially those with T4 node-positive disease.

Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses an analysis of the S-TRAC study in renal cell carcinoma.
 

Dr. George Discusses an Analysis of the S-TRAC Study in RCC

Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses the results of the prospective multicenter Abi Race trial, which compared outcomes of African-American and Caucasian patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (Zytiga) and prednisone. George shared this insight in an interview with 

In prostate cancer in America, African-American men are not only at higher risk for developing prostate cancer, they are also are at high risk for prostate cancer mortality, George explains. This is 2.5 times more likely than it is for Caucasian patients, and a 5 times greater likelihood than Asian-American patients. Researchers suggest there is a genetic component to this, he adds.

In the international COUGAR-AA-302 trial, African-American men were underrepresented; there were 28 African-American patients out of an overall 1100 patients, George says. However, in 15 of the 28 African-American patients who received abiraterone, there were greater and longer response rates by prostate-specific antigen (PSA) compared with the overall population.

In a retrospective, nested, case-control study, researchers from Duke Cancer Institute found this similar pattern with a higher PSA response rate and a longer time to PSA progression in the African-American versus Caucasian patients, demonstrating that African Americans may have greater and more durable responses to abiraterone/prednisone than Caucasian patients.

Daniel J. George, MD, professor of medicine, surgery, member, Duke Cancer Institute, discusses the results of the prospective multicenter Abi Race trial, which compared outcomes of African-American and Caucasian patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (Zytiga) and prednisone.

Dr. George on Results of Abi Race Trial in Prostate Cancer

Daniel J. George, MD, director, GU Oncology, Duke Cancer Institute, discusses the use of sunitinib to treat patients with renal cell carcinoma (RCC).

In the frontline setting, sunitinib has been one of the longest standing VEGF receptor tyrosine kinase inhibitors and is most often used to treat patients who have good or intermediate risk characterizations according to the Motzer criteria, George says.

Sunitinib is different than others in its class, George says, because it is given on an intermittent schedule — usually 4 weeks on and 2 weeks off. The dosing schedule of sunitinib allows for patients to recover from side effects but does not compromise the efficacy of the agent.

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Dr. George on Sunitinib in Renal Cell Carcinoma

Daniel J. George, MD, Director, GU Oncology, Duke Cancer Institute, discusses critical phase III clinical trials in metastatic renal cell carcinoma (mRCC).

The ADAPT study, George says, is looking at patients with newly diagnosed mRCC who have undergone a nephrectomy. Two out of three patients in the study are given a combination therapy of sunitinib malate (Sutent) plus an autologous tumor vaccine called AGS-003. The other arm receives sunitinib alone. As these patients have a more accelerated disease, participation in a study like this could give these patients hope for a better outcome, George says.

Another study, George says, is analyzing the anti-PD-1 antibody nivolumab versus everolimus. George says this study is an important proof-of-concept using an anti-PD-1 in patients who have failed a primary VEGF receptor TKI compared to everolimus, a standard care in mRCC.

The effects of a new VEGF receptor TKI called cabozantinib are also being studied against everolimus, George says. In addition to blocking VEGF, cabozantinib also blocks a MET receptor that may play a role in angiogenesis.

These three trials, George says, will give physicians insight going forward to how to better use these agents and produce better outcomes for patients with kidney cancer.

Daniel J. George, MD, Director, GU Oncology, Duke Cancer Institute, discusses critical phase III clinical trials in metastatic renal cell carcinoma.

Dr. George on Critical Clinical Trials in Kidney Cancer

Daniel J. George, MD, the director of GU Oncology at the Duke Cancer Institute, discusses the potential to incorporate radium-223 (Xofigo) into combination strategies as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC).

In general, George notes, radium-223 is a fantastic drug for combinations because of its favorable toxicity profile. Additionally, he notes, the agent is not being delivered at its maximum tolerated dose, which adds to its potential in combinations.

Many of the toxicities associated with radium-223 are gastrointestinal-related and do not overlap with those seen with other treatments, such as abiraterone acetate or enzalutamide, George notes. However, for chemotherapies, such as docetaxel, sequencing may be more effective than combinations, unless there's a large soft tissue component with symptomatic bone metastases, George believes.

Daniel J. George, MD, from the Duke Cancer Institute, discusses the potential to incorporate radium-223 into combination strategies to treat patients with metastatic castation-resistant prostate cancer.

Dr. George on Radium-223 in Combinations for mCRPC

Daniel J. George, MD, the director of GU Oncology at the Duke Cancer Institute, elaborates on the incorporation of radium-223 (Xofigo) into the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

In May 2013, radium-223 (formally known as Alpharadin) was approved by the FDA for the treatment of symptomatic mCRPC that spread to the bones. Most patients with metastatic disease, George notes, develop modest degrees of bone pain and the vast majorities have symptoms associated with bone metastases. As a result, treatment with radium-223 is appropriate across a broad population.

Overall, George recommends the utilization of radium-223 before chemotherapy for patients with bone predominant patterns and minor symptoms. Inversely, he notes, patients with more extensive soft tissue disease should receive chemotherapy first. Moreover, he notes, the overarching treatment decision can be personalized based on several characteristics. As an example, a patient with heavier clinical deconditioning should receive radium-223 before chemotherapy; however, in more robust patients, chemotherapy may be administered first.

Daniel J. George, MD, from the Duke Cancer Institute, elaborates on the incorporation of radium-223 into the treatment of patients with metastatic castration-resistant prostate cancer.

Daniel J. George, MD

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