The results of recent clinical trials evaluating vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-TKIs) in the adjuvant setting for high-risk renal cell carcinoma (RCC) created uncertainty and controversy as opposed to clarity regarding best treatment strategies. In a recent review article in the Journal of Clinical Oncology, Haas and colleagues explored the trial results and deciphered what they mean for the treatment of patients with high-risk RCC.1

Results from 4 adjuvant VEGF-TKI RCC trials have been reported. One trial reported improved disease-free survival in patients on VEGF-TKI while 3 trials reported no improvement in disease-free survival; no trials reported improvement in overall survival for patients on VEGF-TKI. Not all adjuvant VEGF-TKI trials have reported mature data, but so far “high numbers” of patients have experienced adverse events of grade 3 or higher while on VEGF-TKI, the review authors wrote.

Adjuvant trials are underway to evaluate immune checkpoint inhibitors in high-risk RCC but are still accruing patients. The trials must be completed, the review authors cautioned, in order to determine the benefit of immune checkpoint inhibitor therapy in this high-risk patient population.

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Given the current evidence, the review authors recommend approaching patients with primary tumors with undetermined histology greater than or equal to 7 cm or regional adenopathy about enrolling in the PROSPER trial. If patients have resected clear-cell RCC tumor with disease of at least pT2, they recommend suggesting the patient enroll in InMotion 010, Keynote-564, or Checkmate-914.

“All patients with [greater than or equal to] pT3 disease should also be informed about the [U.S. Food and Drug Administration] approval of adjuvant sunitinib as well as the negative results of ASSURE, PROTECT, and ATLAS and the potential adverse effects of VEGF-TKI and immune checkpoint inhibitor therapy,” the study authors concluded.


  1. Haas NB, and Uzzo RG. Perioperative therapy in renal cell carcinoma: What do we know, what have we learned, what’s next? [published online October 29, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.78.9131