The Predictive Value of Programmed Death Ligand 1 in Patients with Metastatic Renal Cell Carcinoma Treated with Immune-checkpoint Inhibitors: A Systematic Review and Meta-analysis

Immune-checkpoint inhibitors (ICIs) are a mainstay treatment of metastatic renal cell carcinoma (mRCC). As not all patients benefit from ICIs, a biomarker-driven clinical decision-making strategy is desirable.To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs.Multiple databases were searched for articles published up to April 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), or progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were eligible.Six studies matched our eligibility criteria. Treatment with ICIs was associated with significantly higher ORRs and CRRs, and lower PDRs in patients with PD-L1-positive tumors than in those with PD-L1-negative status (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.48-2.28; OR 3.11, 95% CI 2.04-4.75; and OR 0.43, 95% CI 0.31-0.60, respectively). ICI treatment was associated with significantly better PFS in PD-L1-positive patients than in sunitinib-treated patients (hazard ratio 0.65, 95% CI 0.57-0.74), whereas this was not found in patients with PD-L1-negative tumors. Compared with sunitinib, ICI combination therapy improved ORRs and PFS significantly in PD-L1-positive patients of all examined ICIs. Nivolumab plus ipilimumab had the highest likelihood of providing the highest ORR and longest PFS in PD-L1-positive patients.PD-L1 positivity of the tumor is associated with improved ORRs and prolonged PFS in mRCC patients receiving ICI treatment and thus helps identify mRCC patients most likely to benefit from ICI treatment.The use of an immune-checkpoint inhibitor for the treatment of metastatic renal cell carcinoma (mRCC) improved oncological outcomes, and the status of programmed death ligand 1 could contribute to guiding patients and clinicians when determining personalized treatment strategies for mRCC.