Keiichiro Mori1, Mohammad Abufaraj2, Hadi Mostafaei3, Fahad Quhal4, Harun Fajkovic5, Mesut Remzi5, Pierre I Karakiewicz6, Shin Egawa7, Manuela Schmidinger8, Shahrokh F Shariat9, Kilian M Gust4. 1. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 2. Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan. 3. Department of Urology, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 5. Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. 6. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. 7. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 8. Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 9. Department of Urology, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; European Association of Urology Research Foundation, Arnhem, The Netherlands. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
CONTEXT: 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. OBJECTIVE: To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
CONTEXT: 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. OBJECTIVE: To assess the predictive value of programmed death ligand 1 (PD-L1) in mRCC patients treated with ICIs. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
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