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Combinations Continue to Advance RCC Treatment

Danielle Bucco
Published: Thursday, Jan 11, 2018

Rana R. McKay, MD
Rana R. McKay, MD
The treatment landscape for of metastatic renal cell carcinoma (RCC) has rapidly evolved of over the last decade to include more targeted options, and specifically novel immunotherapy regimens, according to Rana R. McKay, MD.

Combination immunotherapy is now at the forefront of clinical studies. In the phase III CheckMate CheckMate-214 trial, for example, nivolumab (Opdivo) and ipilimumab (Yervoy) reduced the risk of death by 32% compared with sunitinib (Sutent).

Furthermore, the results showed that patients with intermediate- and poor-risk disease (75% of the intent-to-treat population) experienced a 37% reduction in the risk of death.1 Based on these findings, the FDA granted a priority review in December 2017 to a supplemental biologics license application for this anti–PD-1/CTLA-4 combination as a frontline treatment for intermediate- and poor-risk patients with advanced RCC.

In an interview with OncLive, McKay, a medical oncologist and assistant professor at the Moores Cancer Center at the University of California, San Diego, discussed the evolving management of patients with advanced RCC, specifically the future of combinations of with immunotherapy regimens.

OncLive: How is the management of advanced RCC evolving?

McKay: The treatment landscape for metastatic RCC has been rapidly evolving over the past 12 years. There have been multiple new agents approved, starting in the VEGF tyrosine kinase inhibitor area, as well as some immunotherapies. The field has been rapidly evolving into looking at combinations of immunotherapy with VEGF- targeted therapy, immunotherapy combinations, and new targets. 

Could you touch on one 1 or two 2 milestones of the past year?

One of the landmark studies of the past couple of years was CheckMate-025. This was a phase III study looking at second-line treatment for patients with metastatic clear- cell RCC. Patients were randomized to receive treatment with nivolumab and everolimus (Afinitor). It was the first time that a treatment in the second-line setting was shown to improve overall survival (OS) for patients with metastatic clear- cell RCC. 

Another landmark study of the past several years was METEOR, which compared the VEGF c-MET inhibitor cabozantinib (Cabometyx) to everolimus. Cabozantinib is the only agent that has been shown to improve OS, progression-free survival, and objective response rates in the second-line setting for patients with metastatic disease. 

Some of the more exciting data that has have recently come out over the past year presented at the 2017 ESMO Congress is the data from CheckMate-214, which is the combination of nivolumab plus ipilimumab versus sunitinib in the front-line space. What we saw from the initial presentations of this trial was that the combination resulted in improved survival and response rates for patients with intermediate- and poor-risk disease. However, those with favorable disease seem to fair better with sunitinib (Sutent). It is going to be exciting how this treatment combination falls into the landscape of RCC.

Can you discuss ongoing trials investigating immunotherapy?

With regards to immunotherapy, the combination of nivolumab and ipilimumab is an interesting study. Nivolumab is a PD-1 inhibitor and ipilimumab is a CTLA-4 inhibitor. The combination has shown efficacy in other solid tumor malignancies, specifically melanoma. In this study, we saw that the combination did improve survival and response rates for patients with intermediate- and poor-risk disease. 

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Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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