Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

Oncologist. 2020 Mar;25(3):252-258. doi: 10.1634/theoncologist.2019-0372. Epub 2019 Sep 9.


Introduction: Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non-clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials.

Materials and methods: We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta-analysis of proportions for ORR and disease control rate (DCR).

Results: Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%-37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%-23.7%) who achieved a complete remission. At a median follow-up of 24.5 monoths (95% CI, 17.7-32.6), median PFS was 4.9 monoths (95% CI, 3.53-10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment-related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD-1/PD-L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%-26.4%) and 53.4% (95% CI, 44.2%-62.5%).

Conclusion: Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted.

Implications for practice: This article reports on the clinical activity and safety of immune checkpoint inhibitors in non-clear cell kidney cancer. The retrospective data with the meta-analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.

Keywords: Immune checkpoint inhibitors; Meta-analysis; Nivolumab; Non-clear cell renal cell carcinoma; Renal cell carcinoma.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Nivolumab / therapeutic use
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A


  • Vascular Endothelial Growth Factor A
  • Nivolumab