Adjuvant nivolumab plus ipilimumab is no more effective than placebo after resection of localized, high-risk renal cell carcinoma (RCC), according to phase 3 results presented at ESMO Congress 2022.
Nivolumab plus ipilimumab failed to prolong disease-free survival (DFS) and resulted in “considerable” treatment discontinuation due to toxicities, according to presenter Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
These results come from part A of the CheckMate 914 trial (ClinicalTrials.gov Identifier: NCT03138512), which included 816 patients with stage II-III clear cell RCC who underwent radical or partial nephrectomy and had a high risk of recurrence.
Patients were randomly assigned to receive nivolumab plus ipilimumab (n=405) or placebo (n=411). At baseline, the median age was 58 (range, 28-83) years in the immunotherapy arm and 57 (range, 29-81) years in the placebo arm. Most patients (71% and 72%, respectively) were men, and most underwent radical nephrectomy (93% in both arms).
The median follow-up was 37.0 months, and the primary endpoint was DFS by blinded independent review committee.
The primary endpoint was not met. The median DFS was not reached in the nivolumab-ipilimumab arm and was 50.7 months in the placebo arm (hazard ratio, 0.92; 95% CI, 0.71-1.19; P =.5347). The 24-month DFS rates were 76.4% and 74.0%, respectively.
In all, 43% of patients discontinued nivolumab-ipilimumab for any reason, and 33% discontinued due to drug toxicity.
The rate of grade 3 or higher treatment-related adverse events (TRAEs) in the nivolumab-ipilimumab arm was 28%. The most common grade 3 or higher TRAEs were diarrhea (4%) and ALT increase (2%).
The most common grade 3 or higher immune-mediated AEs were diarrhea/colitis (5%), hepatitis (3%), hypophysitis (3%), and adrenal insufficiency (3%). Of the patients who developed immune-mediated AEs, 23% received corticosteroids.
There were 4 fatal TRAEs in the nivolumab-ipilimumab arm. These deaths were due to cardiac arrest, immunotherapy-induced diarrhea/colitis, drug-induced myocarditis, and aortic dissection/ischemic cerebral infarction/pulmonary embolism.
“Further analyses are underway to understand the outcome of CheckMate 914 part A,” Dr Motzer said. “Part B, which is investigating adjuvant nivolumab monotherapy, is currently ongoing.”
Disclosures: This research was supported by Bristol Myers Squibb. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Motzer RJ, Russo P, Gruenwald V, et al. Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA4.