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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.


ABSTRACT: 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.

SUBMITTER: Flaifel A 

PROVIDER: S-EPMC6801080 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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.

Flaifel Abdallah A   Xie Wanling W   Braun David A DA   Ficial Miriam M   Bakouny Ziad Z   Nassar Amin H AH   Jennings Rebecca B RB   Escudier Bernard B   George Daniel J DJ   Motzer Robert J RJ   Morris Michael J MJ   Powles Thomas T   Wang Evelyn E   Huang Ying Y   Freeman Gordon J GJ   Choueiri Toni K TK   Signoretti Sabina S  

Clinical cancer research : an official journal of the American Association for Cancer Research 20190801 20


<h4>Purpose</h4>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.<h4>Experimental design</h4>IHC doub  ...[more]

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