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

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.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
2
Department of Data Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
4
Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
5
Department of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
6
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York.
7
Department of Experimental Cancer Medicine, Barts Cancer Institute, London, United Kingdom.
8
Exelixis Inc., South San Francisco, California.
9
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
10
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. ssignoretti@partners.org Toni_Choueiri@dfci.harvard.edu.
11
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. ssignoretti@partners.org Toni_Choueiri@dfci.harvard.edu.
#
Contributed equally

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.

PMID:
31371341
PMCID:
PMC6801080
[Available on 2020-04-15]
DOI:
10.1158/1078-0432.CCR-19-1135

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