Adjuvant Nivolumab Plus Ipilimumab in Localized RCC: Subgroup Analyses of CheckMate 914

Exploratory analyses indicate that tumor grade and sarcomatoid features may influence outcomes with adjuvant nivolumab plus ipilimumab in patients with localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy.

These data are presented at the American Society of Clinical Oncology 2023 Annual Meeting.

Part A of the CheckMate 914 trial showed that adjuvant nivolumab plus ipilimumab does not improve disease-free survival (DFS) compared with placebo in patients with localized RCC at high risk of postnephrectomy relapse.

Robert J. Motzer, MD, and colleagues conducted exploratory analyses to better understand the outcomes in key patient subsets and in those with early nivolumab-plus-ipilimumab discontinuation. Initial study inclusion criteria for the 816 patients were radical or partial nephrectomy with negative margins after 4 weeks and up to 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a N0M0, T2b-T4 N0M0, or any pT N1M0; and no evidence of residual disease or metastases. In part A, patients were randomized to nivolumab plus ipilimumab or an equivalent placebo for 24 weeks or until disease recurrence or unacceptable toxicity.

Exploratory analyses considered DFS by key subsets, including Fuhrman grade, sarcomatoid features, PD-L1 expression, and nivolumab-plus-ipilimumab exposure of ≤6 cycles versus >6 cycles. Safety was assessed by exposure.

After 37 months of median follow-up, subset analyses suggested a DFS benefit for patients receiving nivolumab plus ipilimumab who had Fuhrman grade 4 or sarcomatoid features. Patients who received >6 cycles of therapy trended toward improved DFS compared with patients receiving ≤6 cycles.

Researchers reported that among the 102 patients who received ≤6 cycles, 3% had sarcomatoid features and 20% had Fuhrman grade 4; treatment discontinuation in these patients was due to toxicity (75%), unrelated adverse events (AEs; 6%), patient request (5%), recurrence (4%), consent withdrawal or noncompliance (4%), or other reason (6%). Most patients receiving ≤6 cycles were discontinued without initial dose delay, they added.

Additionally, in the group of patients who received ≤6 cycles, grade 1/2 all-cause AEs were reported in 35% of patients, and 31% of patients discontinued treatment due to grade 1/2 all-cause AEs.

“Exploratory analyses suggest that tumor grade and sarcomatoid features influence outcomes with adjuvant nivolumab plus ipilimumab,” study authors concluded. “Limited nivolumab plus ipilimumab exposure and discontinuation for low-grade adverse events may have contributed to the lack of DFS benefit observed in CheckMate 914 part A.”