David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses trials investigating immunotherapy regimens for patients with renal cell carcinoma (RCC).

There are several phase III upfront randomized trials of immunotherapy that are interesting, says Nanus. One of the issues with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which has shown great efficacy as a treatment in the upfront setting, is the risk of immunologic side effects. It was seen that some of the trials with PD-1/PD-L1 inhibitors plus tyrosine kinase inhibitors may have less toxicity with similar efficacy. In the adjuvant setting, there are 3 or 4 adjuvant trials investigating this strategy.

In December 2017, the FDA granted a priority review to a supplemental biologics license application for the use of the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with RCC. This is based on the phase III CheckMate-214 trial, in which the combination reduced the risk of death by 32% compared with sunitinib (Sutent) for patients with metastatic RCC. The median overall survival was not reached with the combination versus 32.9 months with sunitinib (HR, 0.68; 99.8% CI, 0.49-0.95;

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Dr. Nanus on Trials Investigating Immunotherapy in RCC

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses the role of immunotherapy in the treatment of patients with kidney cancer.

Immunotherapy is a promising therapy for patients with kidney cancer, says Nanus. There are preliminary results from many studies that show exciting results. The use of immunotherapy has a lot of rationale and is generating a lot of excitement, Nanus adds. However, there are questions as to when would be the best time to use immunotherapy. The concept of giving some immunotherapy first so immune system can recognize the tumor, then remove the tumor surgically, and then continuing immunotherapy appears to be an effective strategy.

There is a large trial using 2 cycles of nivolumab (Opdivo), followed by surgery and then the patient is given more nivolumab. Throughout multiple cancer types, there seems to be a role for immunotherapy for high-risk, relapsed patients, especially since the toxicity profile is good, Nanus explains. There will be combination studies of immunotherapy with tyrosine kinase inhibitors. Overall, there is a lot of hope and optimism that immunotherapy is going to improve the outcome of these patients.

Dr. Nanus Discusses Immunotherapy in Kidney Cancer

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses adjuvant therapy for patients with renal cell carcinoma (RCC).

Investigators are asking if there is anything to do for patients with RCC who have a high risk of relapse after surgery other than observation. Nanus says that for a long time, there was no improvement in overall survival in trials of adjuvant therapy. But, recently, a study of sunitinib (Sutent) in patients with high-risk RCC showed an improvement in progression-free survival.

Although there has been no improvement in overall survival yet, the NCCN guidelines changed to offer sunitinib adjuvant therapy as an option for these patients. The FDA then approved the agent for use as an adjuvant therapy in patients with RCC who have received nephrectomy and are at high risk for recurrence. This was based on the phase III S-TRAC trial, in which adjuvant sunitinib prolonged disease-free survival by 1.2 years compared with placebo following nephrectomy.

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses adjuvant therapy for patients with renal cell carcinoma. 

Dr. Nanus Discusses Adjuvant Therapy for RCC

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses managing side effects from immunotherapy in renal cell carcinoma (RCC).

More oncologists are recognizing immune-related side effects of patients being treated with immunotherapy as the treatment becomes more widely available. For patients with RCC, the more prevalent side effects are rashes, nephritis, hepatitis, and adrenal insufficiency, Nanus says.

The community is gaining a better understanding of these side effects, but medical professionals who do not often deal with these drugs, may not know what to do when a patient with cancer being treated on immunotherapy presents with fatigue. Nanus says that internists and other non-oncologists must be aware of these side effects. Additionally, patients should seek counsel from their medical oncologists if they are observing concerning immune-related side effects .

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses managing side effects from immunotherapy in renal cell carcinoma (RCC).
 

Dr. Nanus on Managing Side Effects from Immunotherapy in RCC

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses cytoreductive nephrectomy for patients with renal cell carcinoma (RCC).

There have been a number of retrospective analyses comparing patients who have had a cytoreductive nephrectomy versus those who did not, explains Nanus. It was clear that patients who had a cytoreductive nephrectomy experienced a higher response.

According to Nanus, if a person can undergo a cytoreductive nephrectomy they should have one as the procedure is associated with improved survival.

Dr. Nanus on Cytoreductive Nephrectomy for RCC

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses ongoing studies in the neoadjuvant setting for patients with renal cell carcinoma (RCC).

In the neoadjuvant setting, there has been many studies predominantly looking at anti-VEGF therapies, explains Nanus. These studies are being done to determine if tumor shrinkage and resectability are improved, will outcomes also improve, or are there postoperative complications?

If you look at these studies, the progression-free survival is the same, states Nanus. The clear role is attempting to prevent the need for dialysis by leaving some kidney behind and shrinking the cancer preoperatively.

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Dr. Nanus on Ongoing Studies in the Neoadjuvant Setting for RCC

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine and NewYork-Presbyterian Hospital, discusses ongoing clinical trials exploring immunotherapy agents for the treatment of patients with bladder cancer.

Currently, there is a trial randomizing patients to receive chemotherapy, a PD-1 inhibitor, or a PD-1 agent plus a CTLA-4 inhibitor, Nanus explains. Prior data in melanoma suggest that PD-1 plus CTLA-4 regimens have significant activity; therefore, it is hoped that a similar effect will occur in patients with bladder cancer.

Another interesting area in this field is determining if immunotherapy has a greater benefit in the neoadjuvant or adjuvant setting. Additionally, Nanus questions whether immunotherapy could have a role in patients with superficial bladder cancer. More research is needed to determine what other indications these types of agents could have activity in, he adds.

Dr. Nanus on Clinical Trials Exploring Immunotherapy in Bladder Cancer

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine and NewYork-Presbyterian Hospital, discusses unanswered questions that remain with atezolizumab (Tecentriq) regarding the treatment of patients with metastatic urothelial carcinoma (mUC).

One of the biggest remaining questions with atezolizumab is finding a biomarker to determine which patients are most likely to respond to the agent, Nanus explains. More than one biomarker will likely be needed, he adds.

Additionally, the duration of treatment with atezolizumab has not yet been determined.

David M. Nanus, MD, medical oncologist, Weill Cornell Medicine and NewYork-Presbyterian Hospital, discusses the unanswered questions that remain with atezolizumab (Tecentriq) in patients with metastatic urothelial carcinoma (mUC).

David M. Nanus, MD