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The Predictive Value of Programmed Death Ligand 1 in Patients with Metastatic Renal Cell Carcinoma Treated with
Keiichiro Mori1, Mohammad Abufaraj2, Hadi Mostafaei3
1Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
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.
Insights
Programmed death ligand 1 (PD-L1) positivity predicts better outcomes for metastatic renal cell carcinoma (mRCC) patients treated with immune-checkpoint inhibitors (ICIs). PD-L1 status helps identify patients most likely to benefit from ICI therapy.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Research
Background:
- Immune-checkpoint inhibitors (ICIs) are a standard treatment for metastatic renal cell carcinoma (mRCC).
- Not all mRCC patients respond to ICIs, necessitating predictive biomarkers for treatment selection.
Purpose of the Study:
- To evaluate the predictive value of programmed death ligand 1 (PD-L1) expression in mRCC patients undergoing ICI therapy.
- To determine if PD-L1 status can guide clinical decision-making for mRCC treatment.
Main Methods:
- A systematic review and meta-analysis were conducted following PRISMA guidelines.
- Six studies comparing objective response rate (ORR), complete response rate (CRR), progressive disease rate (PDR), and progression-free survival (PFS) based on tumor PD-L1 status in mRCC patients were included.
Main Results:
- PD-L1-positive mRCC patients showed significantly higher ORRs, CRRs, and lower PDRs with ICI treatment compared to PD-L1-negative patients.
- ICI treatment led to significantly better PFS in PD-L1-positive patients versus sunitinib, but not in PD-L1-negative patients.
- Combination ICI therapy, particularly nivolumab plus ipilimumab, demonstrated the highest likelihood of superior ORR and PFS in PD-L1-positive mRCC patients.
Conclusions:
- Tumor PD-L1 positivity is associated with improved treatment response and prolonged progression-free survival in mRCC patients receiving ICIs.
- PD-L1 expression serves as a valuable biomarker for identifying mRCC patients who are most likely to benefit from ICI therapy.
- PD-L1 status can aid clinicians in personalizing treatment strategies for mRCC.
