Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy

Results from the phase 3 CheckMate 914 trial demonstrated that adjuvant treatment with nivolumab plus ipilimumab did not improve survival in patients with stage II–III localised renal cell carcinoma (RCC) at risk of post-nephrectomy relapse.

Patients with stage II–III localised RCC have a substantial risk of post-nephrectomy relapse [1]. Approved adjuvant therapeutic options include sunitinib (USA only) and pembrolizumab [2]. Previously, dual immune checkpoint blockade with nivolumab and ipilimumab improved long-term survival versus sunitinib in patients with untreated advanced RCC [3]. The current analysis of the CheckMate 914 trial (NCT03138512) evaluated the clinical outcomes of adjuvant nivolumab plus ipilimumab in the setting of resected stage II–III clear-cell RCC with a high risk of recurrence. Prof. Robert Motzer (Memorial Sloan Kettering Cancer Center, NY, USA) presented the results [4].

A total of 816 patients were randomised 1:1 to receive nivolumab (240 mg every 2 weeks, 12 doses) plus ipilimumab (1 mg/kg every 6 weeks, 4 doses) or a placebo after radical of partial nephrectomy with negative surgical margins. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival (OS) and safety. In the case of non-significant DFS endpoints, no formal analysis of OS was to be performed.

With 37.0 months of median follow-up, the primary endpoint of DFS was not met (HR 0.92; P=0.53). DFS rates at 24 months were 76.4% in the nivolumab plus ipilimumab arm versus 74.0% in the placebo arm. Of note, 43% of participants discontinued treatment in the nivolumab plus ipilimumab arm versus 11% in the placebo arm. The incidence of grade ≥3 treatment-related adverse events was 28% and 2% for the nivolumab plus ipilimumab and placebo arms, respectively.

Based on these results, Prof. Motzer concluded that “adjuvant treatment with nivolumab plus ipilimumab does not improve survival in patients with stage II–III localised clear-cell RCC. The safety of nivolumab/ipilimumab in this population is consistent with the known profile of this combination in patients with advanced RCC.”

1. Motzer RJ, et al. J Clin Oncol. 2017;35(35):3916–3923.
2. Powles T, et al. Ann Oncol. 2021;32(12):1511–1519.
3. Motzer RJ, et al. Cancer 2022;128(11):2085–2097.
4. Motzer RJ, 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. Abstract LBA4, ESMO Congress 2022, 09–13 September, Paris, France.

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Posted on 17 November 20226 September 2023