Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma

Int J Urol. 2023 Sep;30(9):746-752. doi: 10.1111/iju.15193. Epub 2023 May 2.

Abstract

Objectives: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC.

Methods: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment.

Results: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN.

Conclusions: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.

Keywords: cytoreductive nephrectomy; immune checkpoint inhibitors; metastatic renal cell carcinoma.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / surgery
  • Cytoreduction Surgical Procedures / adverse effects
  • Cytoreduction Surgical Procedures / methods
  • Humans
  • Ipilimumab / adverse effects
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / surgery
  • Nephrectomy / methods
  • Nivolumab / adverse effects
  • Retrospective Studies

Substances

  • Nivolumab
  • Ipilimumab