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Clinical outcomes of checkpoint inhibitors in metastatic non-clear cell renal cell carcinoma and clear cell renal cell carcinoma with variant features

  • Guy vin Chang,
  • Moataz Ellithi,
  • Radowan Elnair,
  • Jonathan Bleeker

Research Funding

Checkpoint inhibitors (CPI) are a well-established treatment option for advanced clear cell renal cell carcinoma (ccRCC); however, there is a paucity of data on efficacy of CPI on advanced non-clear cell renal cell carcinoma (nccRCC) and ccRCC with variant (sarcomatoid or rhabdoid) features. Recently, small series have demonstrated benefit for CPI in these entities.

We performed a retrospective review of patients with metastatic nccRCC or ccRCC with variant features, who received a single agent CPI (nivolumab or pembrolizumab) or combination therapy (nivolumab and ipilimumab) between Feb 2016 – Oct 2019 at our integrated community-based health system. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). We used Kaplan-Meier survival analysis for PFS and OS.

A total of 26 patients met eligibility criteria; 11 patients with nccRCC (papillary n = 6, chromophobe n = 1, unclassified n = 4), 12 patients with sarcomatoid ccRCC, 2 patients with rhabdoid ccRCC, and 1 patient with both sarcomatoid and rhabdoid features. Sixteen patients received nivolumab, 3 received pembrolizumab, and 7 received a combination of nivolumab and ipilimumab. CPI was halted in 4 patients due to adverse effects including arthralgia, hyperthyroidism, hepatitis, and colitis. Among these 26 patients, 5 patients (19.2%) achieved complete response (CR), 3 patients (11.5%) achieved partial response (PR), and 10 patients (38.5%) had stable disease (SD). All patients who achieved CR or PR had a durable response throughout the follow-up period. At the median follow-up of 16.4 months, median PFS was 14.3 months, and median OS was not reached.

In this retrospective series, the ORR of CPI in metastatic nccRCC and ccRCC with variant features was 30.7%, and disease control rate was 69.2%. These findings suggest that CPI may provide significant clinical benefit in patients with nccRCC and ccRCC with sarcomatoid and/or rhabdoid features. Sample size may limit inference and additional studies are needed.