"In this trial, and in all the major IO/TKI trials, the checkpoint inhibitor stopped at 2 years. In this trial it was about 25% of patients who made it to that time point," says Brian I. Rini, MD.
In this video, Brian I. Rini, MD, discusses the background of the 5-year analysis of the KEYNOTE-426 trial (NCT02853331) in advanced renal cell carcinoma, which was presented at the 2023 ASCO Annual Meeting in Chicago, Illinois. Rini is a professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee.
Could you provide some background on the KEYNOTE-426 trial?
So, just a brief reminder, KEYNOTE-426 was the first IO/TKI versus sunitinib trial to be reported now many years ago. Pembrolizumab plus axitinib was the experimental arm. It reported first, I think, maybe 3 years ago at ASCO GU. Progression free and overall survival advantage and response rate advantage to the combination versus monotherapy, building on the previous [ipilimumab/nivolumab]results and establishing what were about to be a series of IO/TKI trials that showed benefit. There have been a couple of follow-ups since that time at various meetings and publications with 2- and then 3-year minimum follow-up, and we're about to present 5. Those subsequent publications, in essence, confirmed the original benefits seen across those clinically relevant endpoints.
What are some of the notable data being presented at ASCO?
All the endpoints are updated. There's an additional 2 years of follow-up. It's really important because ipi/nivo set the standard and it had a 2-year headstart on the IO/TKI trials, and so as always had the longest follow-up by definition. As we use immune based regimens, this long follow-up, including what happens to people after they stop therapy is extremely important. Again, an additional 2 years of follow-up, 5 years minimum for this particular data set.
We'll see updates across survival and PFS in response. As you can imagine, survival is the most meaningful update. Progression free survival and response rates are pretty much set and haven't changed much since the initial analyses.
The additional data that's being presented, it's been presented a little bit before but expanded on, is what we call Completer analysis. So, in this trial, and in all the major IO/TKI trials, the checkpoint inhibitor stopped at 2 years. In this trial it was about 25% of patients who made it to that time point. So, there'll be data presented about what happens to those patients, who are they, what are their baseline characteristics, what happens to them. Which is particularly important in practice, because in my own practice, and I'm sure many people are starting to see more and more of these patients who get to the 2-year mark, and you're having conversations with patients about should I stop? And what happens? And, you know, what are my [adverse] effects if I stop, or if I don't stop? You're making those clinical decisions, so I think we need more data for that particular cohort.