Long-Term Data on IO/IO in RCC Shows Intriguing Results for Favorable Risk

Alan Tan, MD, assistant professor of medicine in the division of hematology and oncology at Vanderbilt University Medical Center, discusses the 8-year follow-up data from the CheckMate 214 trial (NCT02231749) of patients with advanced renal cell carcinoma (RCC).

The phase 3 CheckMate 214 trial investigated the combination of ipilimumab (Yervoy) plus nivolumab (Opdivo) compared with sunitinib (Sutent). It was the only dual immunotherapy (IO) trial in the front line, compared with 3 other regimens combining IO with tyrosine kinase inhibitor (TKI). It had 3 primary end points of overall response rate, progression-free survival (PFS), and overall survival (OS) focused on the patients with intermediate or high risk by International Metastatic RCC Database Consortium (IMDC) risk status.

At 8 years of follow-up, approximately one-third of patients had a durable remission and are mostly not receiving treatment, Tan noted. The trial led to FDA approval only in patients with intermediate- or high-risk disease because of the study design, but over time, the patients with favorable risk also demonstrated an HR of 0.82 favoring IO/IO. Though this is an exploratory post hoc analysis, Tan says that this combination seemed to perform better in the favorable-risk group than IO/TKI combinations in terms of HR.

TRANSCRIPTION:

0:10 | We now have 8-year follow-up from the first IO combination trial of CheckMate 214. It's the only one out of the four main ones that I would say is immunotherapy-only based. So IO/IO is how we like to refer that to, and it's ipilimumab plus nivolumab. Essentially this study had an interesting 3 coprimary end points. It's looking at ORR, PFS, and also OS in the intermediate and poor-risk population. But then they looked at all IMDC in the secondary end points as well.

Essentially, what we've seen over 8 years now is that you have a continued tail of the curve. About a third of the patients in the intention to treat population are still doing well. They're alive and probably mostly off treatment. So we see a durable remission. The FDA approved this combination for intermediate- and poor-risk only. But interestingly, we now see, after 5 years, that the curves are starting to cross over in even [favorable] risk. So you're still seeing an HR of [0.82], which is probably the better HR that that we're seeing, compared [with] the IO/TKI combinations, which actually are either above 1 or close to 1.