Introduction: Immunotherapy is becoming the main management option for metastatic renal cell carcinoma. These treatments are increasingly being trialled in the adjuvant setting after surgery. There is no consensus on which agent, if any, improves outcomes when used as adjuvant treatment following nephrectomy for renal cancer. We performed a systematic review and network-meta-analysis of systemic agents used in the adjuvant setting after surgery for kidney cancer.
Methods: We performed a systematic review in accordance with PRISMA guidelines. We included patients with RCC that has been completely resected. Patients with metastatic disease were excluded. We included all adjuvant systematic therapies that were commenced within 90 days of renal surgery. We only included randomised studies. We performed a network meta-analysis of all included trials which enables indirect comparisons of treatments based on a common comparator arm using a frequentist approach.
Results: We included thirteen studies with the following adjuvant therapies: Axitinib, Girentuximab, interferon-alpha, interleukin-2, Pazopanib, Pembrolizumab, Sorafenib, Sunitinib and Thalidomide. Only pembrolizumab [HR 0.74, 95%CI 0.57-0.96] and pazopanib [HR 0.80, 95%CI 0.68-0.95] prolonged time to disease recurrence compared to observation. These two treatments were the two highest ranked comparisons with a P-score of 0.87 and 0.80, respectively. None of the agents demonstrated an overall survival benefit compared to observation.
Conclusions: Pembrolizumab and pazopanib were the only two adjuvant agents that improved time to disease recurrence compared to observation, with the former likely being the most efficacious. None of the treatments improved overall survival and almost all increased severe adverse events.