Background Non-clear cell renal cell carcinoma (nccRCC) represents around 25% of RCC variants. However, most data about use of nivolumab and ipilimumab (nivo-ipi) in kidney cancer comes from one trial in clear cell RCC (ccRCC).1 In a recent post-marketing study, CheckMate-920, involving 46 patients with nccRCC, nivo-ipi had an objective response rate (ORR) of 19.6%.2 Here, we aim to report real world experience with combination nivo-ipi in nccRCC.
Methods Between 2017 and 2022, 48 patients (pts) with nccRCC were treated with nivo-ipi at our center. Toxicity, ORR and overall survival (OS) were retrospectively evaluated. Response was assessed by two board-certified radiologists. Median OS and follow up were calculated from the start of nivo-ipi using the Kaplan-Meier method. 95% confidence interval was calculated using the Clopper-Pearson Method.
Results The majority of patients (92%) received nivo-ipi as first-line therapy and 40% had prior nephrectomy. Histological variants included: papillary (35%), chromophobe (19%), and unclassified (46%) (table 1). 33% of pts had sarcomatoid features (SF). ORR was 41% for papillary, 22% for chromophobe, and 32% for unclassified. Response among pts with SF was 12/16 (75%). Median follow-up from nivo-ipi start was 27.2 months (mo) (95% CI: 17.5–38.7). Median OS was 25.7 mo (95% CI: 11.9–54.8) months, with 54.8 mo (12.7–54.8) for papillary, 28.3 mo (95% CI: 0.6-Undefined) for chromophobe, and 11.9 mo (95% CI: 3.2-Undefined) for unclassified. Among patients with unclassified variants, median OS was improved for patients with presence of SF versus those without (HR=0.10; 95% CI: 0.03–0.33; p = 0.005). 31% of pts developed Grade 3–4 toxicity with pneumonitis (n=5), colitis (n=3), hepatitis (n=3), immune-mediated glomerulonephritis (n=2), rash (n=1), pancreatitis (n=1), ITP (n=1), and anaphylaxis (n=1). There were no reported Grade 5 toxicities.
Conclusions Nivo-ipi demonstrated a favorable efficacy/toxicity profile in nccRCC, especially among the papillary varient. Pts with unclassified variant without SF had a high upfront PD rate and low median OS. Consistent with ccRCC, SF enriched for clinical benefit from nivo-ipi in nccRCC. Understanding the driving immune biology of nccRCC is necessary for optimizing the use of novel therapy combinations.
Motzer Robert, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma. New England Journal of Medicine. 2018; 378,14: 1277–1290.
Tykodi Scott S, et al. Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carnioma: results from the phase 3b/4 CheckMate 920 trial. J Immunonother Cancer. 2022; v10.
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