Lenvatinib Plus Pembrolizumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma (aRCC)
Robert Motzer, MD, presents the overall survival analysis data from the 4-year follow-up of the CLEAR study in patients with advanced renal cell carcinoma.
Robert Motzer, MD: Good afternoon. My name is Robert Motzer, and I'm from Memorial Sloan Kettering Cancer Center. I'm a GU medical oncologist, and I'm joined here by Moshe Ornstein, MD, and Dr Brian Rini.
Moshe Ornstein, MD: Hi, I'm Moshe Ornstein, MD. I'm a GU oncologist at the Cleveland Clinic where I specialize in renal cell carcinoma. Delighted to be here today to discuss updates in clear cell RCC from ASCO 2023.
Dr. Brian Rini: I'm Brian Rini, also GU medical oncologist and Chief of Clinical Trials at Vanderbilt-Ingram Cancer Center. It's good to be here.
Robert Motzer, MD: So today we're going to do a presentation and the discussion around different aspects of the abstracts that were presented at ASCO. And we'll start with the frontline treatment updates, which was an important part of the ASCO meeting. Regarding standard of care and state of the art, the NCCN guidelines highlight a number of IO combinations as preferred category one. These include lenvatinib, pembrolizumab, cabozantinib, nivolumab, and axitinib + pembrolizumab as preferred regimens for favorable risk. And for the poor and intermediate risk the preferred category one regimens are axitinib + pembrolizumab, cabozantinib + durvalumab, and ipilimumab + durvalumab, as well as lenvatinib + pembrolizumab. At this year's ASCO, there was important updates for long-term follow-up for two of these studies.
The first was the long-term final prespecified overall survival analysis for the CLEAR trial, and this was done with a four-year follow-up. And the results of this study summarized the outcomes for lenvatinib + pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma. The study of the schema of the trial was that patients with previously untreated RCC were randomized actually to three different arms. Lenvatinib + pembrolizumab, lenvatinib + everolimus or sunitinib. The primary endpoint was progression-free survival and important secondary endpoints included overall survival and response rate. In this trial, lenvatinib + pembrolizumab met primary endpoint for progression-free survival and overall survival compared to sunitinib. In contrast, lenvatinib + everolimus, while meeting the primary endpoint of progression-free survival, did not meet the overall survival endpoint and had considerable toxicity. And so, this was not followed through with regulatory approval and is not a part of our standard of care today. The focus of this presentation was the four-year follow-up results for the lenvatinib + pembrolizumab arm compared to sunitinib. In this long-term follow-up, the results showed that the progression-free survival benefit for lenvatinib + pembrolizumab versus sunitinib was durable with a median progression-free survival of almost 24 months, the longest that we've seen in any study to date with renal cell carcinoma. The hazard ratio remained in favor of lenvatinib + pembrolizumab over sunitinib with a hazard ratio of 0.47. Most importantly, there was a durable survival benefit as well. For this prespecified analysis, the median overall survival for lenvatinib + pembrolizumab was almost 54 months and the hazard ratio was 0.79 in favor of lenvatinib + pembrolizumab over sunitinib. One of the more interesting analyses that was performed was the survival according to response. The responders were grouped by complete response, partial response with greater than 75% reduction in tumor, and other partial response as well as stable disease. What was found is that there was overall striking survival for patients who had had a complete response or what we refer to as a deep PR or near PR on this program.
