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November 21, 2018

Emerging Role of Combination Immunotherapy in the First-line Treatment of Advanced Renal Cell CarcinomaA Review

Author Affiliations
  • 1Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
  • 2Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio
  • 3Department of Internal Medicine, UT Southwestern, Kidney Cancer Program, Dallas, Texas
JAMA Oncol. Published online November 21, 2018. doi:10.1001/jamaoncol.2018.4604

Importance  Novel immunotherapies, notably the immune checkpoint inhibitors, have been shown to be efficacious in patients with advanced renal cell carcinoma, but innate or adaptive resistance is observed with single-agent immunotherapy. New combination treatment strategies are needed that can improve efficacy in a broader patient population, without exacerbating the toxic effects.

Observations  Numerous late-phase trials are ongoing to investigate (1) dual immune checkpoint inhibition or (2) combined inhibition of immune checkpoints and vascular endothelial growth factor. Initial results from studies of the nivolumab plus ipilimumab and atezolizumab plus bevacizumab combinations have demonstrated efficacy compared with sunitinib malate in treatment-naïve patients with advanced renal cell carcinoma; moreover, the safety profile of these combinations compare favorably with sunitinib. Nevertheless, immune checkpoint inhibition is associated with unique immune-related adverse events, and practicing physicians must be educated on how to best identify and manage these events.

Conclusions and Relevance  Evidence suggests that immunotherapy-based combination regimens will be an important addition to the treatment of advanced renal cell carcinoma in both the first- and later-line setting; however, clinical study data and clinical practice experience indicate that optimizing the management of the associated immune-related adverse events is essential to maximizing the advantages of these therapies.