Dr George on the CheckMate 8Y8 Trial of Nivolumab With/Without Ipilimumab in Untreated RCC

Daniel J. George, MD, professor, medicine and surgery, Duke Cancer Institute, discusses key results from the phase 3b CheckMate 8Y8 study (NCT03873402) evaluating nivolumab (Opdivo) plus ipilimumab (Yervoy) vs nivolumab monotherapy in patients with previously untreated advanced renal cell carcinoma (RCC).

The randomized, double-blind study was mandated by the European Medicines Agency (EMA) following the approval of ipilimumab and nivolumab for the first-line treatment of adult patients with intermediate/poor-risk advanced RCC, George begins. Although there is existing data showing activity with nivolumab monotherapy in the refractory setting, there was limited information on its efficacy as a single agent in the phase 3 CheckMate 214 trial (NCT02231749), which supported the regimen's approval. Therefore, the EMA requested comparison data to elucidate the contribution of ipilimumab in this combination therapy, George explains.

The study compares standard-of-care ipilimumab followed by nivolumab with nivolumab monotherapy, focusing on progression-free survival (PFS) and overall survival (OS) as end points, George details. However, immunotherapies administered alone may not always produce significant changes in radiographic PFS (rPFS), despite their potential benefit for patients, he notes. This presents challenges in comparing rPFS between the 2 treatment arms.

Given the nature of immunotherapy response patterns and the size of the study (approximately 430 patients), longer-term outcomes may provide clearer insights into the efficacy of the combination regimen, George continues. The hope is to identify a benefit associated with the ipilimumab-nivolumab combination, with an expectation that ipilimumab adds to the treatment's efficacy, George states.

Recent data presented at the 2023 ASCO Meeting, including the 8-year updated data from CheckMate 214, have shown durable responses with the combination regimen, particularly in patients with intermediate and poor-risk disease, George adds. This underscores the potential benefit of the combination therapy, although further analysis from CheckMate 8Y8 will be crucial in substantiating these findings and understanding any limitations in the trial design that may impact clinical outcomes, George concludes.