Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis

Keiichiro Mori, Hadi Mostafaei, Noriyoshi Miura, Pierre I. Karakiewicz, Stefano Luzzago, Manuela Schmidinger, Andreas Bruchbacher, Benjamin Pradere, Shin Egawa, Shahrokh F. Shariat

Research output: Contribution to journalReview articlepeer-review


Purpose: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. Materials and methods: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. Results: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73–0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75–0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76–0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74–0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. Conclusion: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy–tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs.

Original languageEnglish
Pages (from-to)265-273
Number of pages9
JournalCancer Immunology, Immunotherapy
Issue number2
Publication statusPublished - Feb 2021
Externally publishedYes


  • First-line
  • Immune-checkpoint inhibitors
  • Network meta-analysis
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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