Introduction: Genomic features linked to prediction of response to immunotherapy in metastatic renal cell carcinoma (mRCC) are still lacking. Protein polybromo-1 (PBRM1) mutations have been studied as a potential biomarker of clinical benefit, with conflicting published data so far. Material and Methods: This systematic review was guided by the standards of the PRISMA statement to identify studies involving mRCC, immunotherapy and mutations in PBRM1. The main objective was to assess the relationship between PBRM1 mutations and response to immune checkpoint inhibitors (ICI) in patients with mRCC. Results: After an initial search that identified 422 studies, 8 studies met the eligibility criteria and were selected for the final analysis. Data are included from 2 trials in the first-line treatment setting, and 6 trials in second- or later treatment lines evaluating the relationship between the presence of PBRM1 mutations and clinical benefit (CB) with ICI treatment. Regarding the first-line treatment setting, the analysis of both studies failed to show any CB in patients with PBRM1 mutations treated with ICI. However, for the second- and later treatment lines, the results were mixed. Conclusions: PBRM1 mutations may be a potential genomic biomarker to predict response to ICI treatment in patients with mRCC, mainly in second- and later treatment lines, but the existence of conflicting data in the literature highlights an important bias in the studies and the need for additional clinical validation in large, prospective trials.
Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma: a systematic review and indirect comparison of clinical effectiveness
