Advanced Clear Cell RCC with Intermediate-Risk and the CHECKMATE-214 Trial
Nizar Tannir, MD, presents the case of a 57-year-old patient with intermediate-risk advanced clear cell RCC, and Scott Tykodi, MD, PhD, presents data from the CheckMate 214 trial.
Nizar Tannir, MD: Let me go through the second case. We’re going to talk about intermediate risk. We already talked about all of the risks in our discussion. I’ll quickly go through the second case, and then I’ll give you the floor again, Scott, to go through CheckMate 214 (NCT02231749) data¼that will be a good segue for that piece.
This is a 57-year-old patient diagnosed with clear cell RCC [renal cell carcinoma]. There were no sarcomatoid features. The patient underwent a right nephrectomy in March 2020. Ten months later, he developed metastatic disease in both lungs and retroperitoneal [lymph nodes], and was diagnosed with stage IV RCC with metastasized lungs and retroperitoneum. The patient’s performance status is 80%. Laboratory results are good except for elevated corrected serum calcium level. The patient had a recurrence within a year of initial diagnosis and has hypercalcemia, so by IMDC [International Metastatic RCC Database Consortium] risk criteria, he has intermediate-risk disease. The treating physician elected to start this patient on nivolumab-ipilimumab. I’ll turn it over to you, Scott, to take us through the data from CheckMate 214.
Scott Tykodi, MD, PhD: Excellent. CheckMate 214 was nivolumab plus ipilimumab in advanced RCC vs the comparator sunitinib, most people are probably aware. It was the first IO [immunotherapy] doublet comparison with sunitinib with a positive outcome, and the first FDA approval of frontline checkpoint immunotherapy. This is a very influential data set. It has the longest follow-up of all the frontline regimens as well. It’s a little ahead in showing us some of the long-term outcome end points as well.
This was a frontline regimen, so patients couldn’t have prior therapy. This study enrolled only for clear cell histology, and some of the other standard features: you had to have measurable target disease and good performance status. The stratification factors are shown here by risk score. It’s important to remember that CheckMate 214 allowed enrollment of all risk categories, but the primary end point was focused on intermediate and poor risk. Patients were stratified by region as well.
Regarding the treatments, the investigational arm was the IO doublet, nivolumab dosed 3 mg/kg plus ipilimumab 1 mg/kg in the combination phase, times 4 doses, and then ongoing nivolumab, initially weight-based dosing and converted over time to a fixed…and milligram dosing. Arm B was sunitinib in a conventional way, 50-mg daily starting dose for 4 weeks on, 2 weeks off. Shown at the bottom are the primary end points: response rate, progression-free survival, and overall survival. The primary analysis end point was intermediate and poor-risk patients. The secondary end point was all risk categories by intent to treat.
In regard to baseline characteristics, for a large, randomized study, we expect things to be very comparable. The risk categories shown are well balanced between the groups, and the regional involvement was also generally pretty well balanced.
[Let’s look at] overall survival by the intent-to-treat population. Shown here is the median survival. Maybe Nizar can jump in here. I believe some of these data were taken from an ESMO [European Society for Medical Oncology Congress] presentation. That wasn’t a true median survival. I believe it was a conditional survival end point. As of the last update of ipilimumab-nivolumab, we have median for intermediate or poor risk of 47 months vs 26 months. I believe the median for sunitinib intent-to-treat was 38.4 months. I’m not certain the other medians have been defined in a conventional way at this point. The hazard ratios are at the bottom. There was a strong hazard ratio for ipilimumab-nivolumab vs sunitinib in the primary analysis cohort, intermediate or poor risk. In favorable risk, as you look at the Kaplan-Meier curves, it still runs very close, and clearly the hazard ratio overlaps 1.0.
In terms of safety, given the presence of this regimen for renal cell and other diseases, most practitioners are pretty familiar with checkpoint toxicities. I don’t think there’s anything particularly novel or unique about the renal cell cohort vs melanoma, lung cancer, or others. As far as high-risk toxicity, you see some diarrhea and skin [involvement]. The lipase elevations, which are a curiosity of this regimen, are often without associated clinical symptoms. But I don’t think there’s anything highly unique for a renal cell audience to pay attention to or focus on.
Transcript edited for clarity.
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