PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN

Clin Cancer Res. 2019 Oct 15;25(20):6080-6088. doi: 10.1158/1078-0432.CCR-19-1135. Epub 2019 Aug 1.


Purpose: Programmed death-ligand 1 (PD-L1) status by IHC is prognostic in metastatic renal cell carcinoma (mRCC), and its role as a potential predictive biomarker is under investigation. Using tumor tissue from the METEOR (NCT01865747) and CABOSUN (NCT01835158) clinical trials, we explored whether PD-L1 expression and the extent of the immune cell infiltrate can serve as prognostic and/or predictive biomarkers for cabozantinib and other targeted agents.

Experimental design: IHC double staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on tumor tissue from METEOR (n = 306) and CABOSUN (n = 110) clinical trials. Immune cell density and MET expression levels were also analyzed. Our primary aim was to correlate progression-free survival (PFS) by independent central review with PD-L1 status in patients treated with cabozantinib, everolimus (METEOR), or sunitinib (CABOSUN). Overall survival (OS) was also interrogated.

Results: Tumor cell (TC) PD-L1 expression (≥1% cutoff) was detected in 29% and 23% of tumors from patients in the METEOR and CABOSUN trials, respectively. On univariate analysis, patients with PD-L1-positive TC had poorer PFS and OS than patients with PD-L1-negative TC on both trials, independent of therapy. On multivariable analysis and when combining the two trials, the association between TC PD-L1 expression and OS was statistically significant for all patients (P = 0.034) and for patients treated with cabozantinib only (P = 0.038). Cabozantinib was associated with improved PFS (HR < 0.70) and OS (HR < 0.85) compared with everolimus and sunitinib irrespective of PD-L1 expression.

Conclusions: Higher PD-L1 expression results in worse clinical outcomes in mRCC treated with targeted therapy. Furthermore, PD-L1 expression is not predictive of response to cabozantinib therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anilides / therapeutic use
  • B7-H1 Antigen / analysis
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy*
  • Chemotherapy, Adjuvant / methods
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Everolimus / therapeutic use
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Multicenter Studies as Topic
  • Nephrectomy
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Sunitinib / therapeutic use


  • Anilides
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Protein Kinase Inhibitors
  • Pyridines
  • cabozantinib
  • Everolimus
  • Sunitinib

Associated data

  • ClinicalTrials.gov/NCT01865747
  • ClinicalTrials.gov/NCT01835158