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Pembrolizumab outperforms tyrosine kinase inhibitors in the adjuvant therapy of patients with high-risk renal cell carcinoma

Despite radical nephrectomy for non-metastatic renal cell carcinoma (RCC), up to 40% of patients experience disease relapse.1 Adjuvant systemic therapy, however, has been not widely used to reduce this risk.2,3 Despite the benefit of tyrosine kinase inhibitors (TKIs) as systemic therapy for metastatic RCC, the data on their efficacy in the adjuvant setting for non-metastatic RCC remains controversial, atbest.4-10 The lack of significant survival benefits along with the significant side effect profile of TKIs poses a challenge to their use inthe adjuvant setting (i.e., overtreatment risk and limited tolerability).5,11

Recently, immune checkpoint inhibitor (ICI) therapies have been tested and approved in the metastatic RCC setting.12,13 Given their favorable adverse event (AEs) profile, they have been tested in the adjuvant setting in patients of increased risk for relapse after nephrectomy in the first phase III randomized clinical trial KEYNOTE-564 (pembrolizumab).14 Given the lack of data on risk/benefit comparison of ICIs and TKIs in adjuvant RCC setting, we performed a systematic review and network meta-analysis (NMA) of phase III RCTs to compare the oncologic and toxicity outcomes of adjuvant ICIs and TKIs in post-nephrectomy patients with localized and locally advanced RCC.15 Six trials (KEYNOTE-564, S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our analysis (Tab. 1).

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