David M. Nanus, MD
The inclusion of neoadjuvant and adjuvant therapy in the treatment of patients with renal cell carcinoma (RCC) may reduce the risk of recurrence after surgery, said David M. Nanus, MD. Specifically, tyrosine kinase inhibitors (TKIs) and immunotherapy are showing benefit as adjuvant treatment options for patients with high-risk disease.
After the NCCN guidelines were updated to include adjuvant sunitinib (Sutent) as an option for patients with high-risk disease, the FDA approved the agent in that setting. This approval 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 in patients who were at high risk for recurrence.
Immunotherapy is demonstrating benefit in a number of other genitourinary cancers and has shown improved progression-free survival (PFS) in RCC. Nanus said that it is the most exciting advance in RCC to date, although overall survival (OS) data have yet to confirm this.
Moreover, Nanus, said that although surgery is still a vital part of the treatment of RCC, its pairing with TKIs or immunotherapy may offer a prolonged benefit for high-risk patients.
In an interview with OncLive®
, Nanus, a medical oncologist at Weill Cornell Medicine/NewYork-Presbyterian Hospital, discussed the promise of immunotherapy and the continued role of surgery in the treatment in RCC.
OncLive: Can you discuss the issue of neoadjuvant and adjuvant therapy in patients with kidney cancer?
: There have been many studies over the years, dating back 3 or 4 decades, trying to improve the outcomes for patients with renal tumors. These are generally large tumors that have invaded the vena cava that have a higher risk of relapse after surgery. Can we do anything to reduce that risk of relapse? For the longest time, we had no benefit—meaning that all of these randomized trials never showed an improvement in OS. Many of these studies are from the cooperative groups, specifically studies with sunitinib, pazopanib (Votrient), and sorafenib (Nexavar).
More recently, one study did show a benefit for patients in terms of PFS. These are patients with T3 and T4 kidney cancer—a very high-risk subset. This showed that there was an improvement in PFS. Meaning, the patients who went on sunitinib for about 1 year seemed to have a lower risk of progression. Although, there was no improvement in OS, so patients haven't yet seemed to live any longer. There is continued follow-up. Based on those data, the NCCN guidelines changed, making this an option for treatment. You could still do observation, or you could consider giving sunitinib adjuvant therapy.
What treatments in RCC seem to be the most promising?
What may be most promising is immunotherapy. It could be combined in the future with a TKI—some of those studies in advanced-stage patients have showed impressive preliminary results. The use of immunotherapy has a lot of rationale and is generating a lot of excitement. There are questions in terms of when to use immunotherapy. In preclinical models, the concept of giving immunotherapy while the tumor is still there—so that their immune system actually recognizes the tumor antigens—then removing the tumor surgically and continuing immunotherapy seems to be one of the more effective strategies. There are a number of trials using that rationale.
In lung cancer, bladder cancer, and other tumor types, we are seeing efficacy in high-risk relapsed patients. The toxicities tend to be less. If you look at all of the TKI studies, there was, almost universally, a dose reduction because of adverse events (AEs). With immunotherapy, many patients have minimal AEs, and only some have severe AEs. That is the most exciting area, and there will be future studies of combination TKIs and immunotherapy. There is a lot of hope and optimism that we are going to improve outcomes for patients with T3, T4, and bulky T2 disease.
Are there certain toxicities that physicians should be looking out for, or telling their patients to be aware of with immunotherapy agents?
There is more of a recognition of AEs by the community oncologist who commonly handles immunotherapies. The general internist doesn't understand it. I have had cases where patients have gone to the emergency room and don't know what's going on. They get admitted and then they reach out to me, and I say, "Oh, you have adrenal insufficiency. You have to do this and that."