Pedro C. Barata, MD, MSc, reviews the data from the KEYNOTE-426 trial, which focused on axitinib with pembrolizumab.
Tian Zhang, MD: I’d love to move onto another one of our approved combinations in the front-line setting. The axitinib [Inlyta] and pembrolizumab [Keytruda] combination. Dr Barata, I wonder if you can give us some updates about the KEYNOTE-426 trial from which axitinib and pembrolizumab was approved.
Pedro C. Barata, MD, MSc: Sure. I’m happy to do so. Just a reminder. KEYNOTE-426 was another phase 3 trial that basically took patients with advanced renal cell carcinoma and randomized them to either sunitinib [Sutent], which was the standard of care at the time, or a combination of pembrolizumab with axitinib standard doses. This trial initially ran around 12 months follow-up. It was significant or positive for dual primary end points at the time with progression-free survival and overall survival. It met both end points. It got approved based on that. We started treating patient with that combination regimen. After 2019, when the data was initially presented by Dr. Brian Rini, MD, and Dr … ‘s team. Really, the question about the importance of the long-term follow-up is whether or not those results are confirmed if you will. We got this data with 42-month follow-up presented by Dr. Rini last year. It’s really interesting from the efficacy perspective and also from the safety perspective. From the efficacy perspective, we got again confirmation of very interesting results. High response rate around 60% or so, including about 10% complete responses. But also positive for progression-free survival [PFS] and overall survival with risk reduction that was around 30% or a bit more. Definitely active and is all favoring the combination of axitinib and pembrolizumab. Now, concerning your question regarding safety, we all know that when we use this combination regimen, we do expect a safety profile that combines both adverse events in relation to TKIs [tyrosine kinase inhibitors] via therapies and I’m thinking about diarrhea, hand-foot syndrome, high blood pressure, but also fatigue, etc. But also, immune-related adverse events that are more related with immune checkpoint inhibitors. In this case, pembrolizumab. I’m thinking probably 1 of the most common was hypothyroidism here. But other side effects, such as rash, diarrhea as well, and other immune-related adverse events can happen. I should just mention that it was really clever the way they designed this study because they allow dose titration specifically for the TKI. We could go up with the dose of axitinib, actually Dr … helped develop that data with dose escalation with axitinib. And that was actually incorporated in his design. You could go up on the dose and actually you could also down, titrate it down, to 3 and then 2 mg b.i.d. which really, I believe, allowed to remain patients on treatment and while the regimen was active. In reality, when you look at dose continuation of both agents was low. Around 10% or so. Either agent was discontinued around 30% or so. In general, the safety profile was very favorable. There were no new signals. Safety signals at 42 months of follow-up. Thus, according to what we saw early on, I would say from efficacy and safety profile this combination regimen continued to demonstrate value and continued to help patients in this first-line setting.
Tian Zhang, MD: Wonderful summary and your approach to adverse event management in titrating the drug and making sure that our patients are tolerating well and staying on treatment. Wonderful.
This transcript has been edited for clarity.