Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib A Distinct Phenotype Independently Associated With Low PD-L1 Expression

Abstract : BACKGROUND: Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.PATIENTS AND METHODS: In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed. Immunohistochemistry (carbonic anhydrase IX, vascular endothelial growth factor, c-MET, programmed death-ligand 1 [PD-L1], and PD-1) and VHL status were performed. Progression-free survival and overall survival were calculated from sunitinib introduction and from progression. LTRs and their corresponding tumors were compared with others using univariate and multivariate analysis.RESULTS: Twenty-eight patients were LTRs. They had a median progression-free survival of 28 months versus 4 months for other patients (P < .001). Similarly, LTRs had a median overall survival of 49 months versus 14 months (P < .001), even from progression (median, 21 vs. 7 months; P = .029). They were associated with a favorable or intermediate risk (International Metastatic Renal Cell Carcinoma Database Consortium model) (P = .007) and less liver metastasis (P = .036). They experienced more frequent complete or partial responses at the first radiologic evaluation (P = .035). The corresponding ccRCCs were associated with less nucleolar International Society for Urological Pathology grade 4 (P = .037) and hilar fat infiltration (P = .006). They were also associated with low PD-L1 expression (P = .02). Only the International Metastatic Renal Cell Carcinoma Database Consortium model and PD-L1 expression remained significant after multivariate analysis (P = .014 and P = .029, respectively).CONCLUSION: Primary tumor characteristics of LTRs were studied for the first time and demonstrated a different phenotype. Interestingly, they were characterized by low expression of PD-L1, suggesting a potentially lower impact of targeted immunotherapy in these patients.
Complete list of metadatas

Cited literature [6 references]  Display  Hide  Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-02076598
Contributor : Xavier Chard-Hutchinson <>
Submitted on : Monday, April 15, 2019 - 11:12:06 AM
Last modification on : Tuesday, July 23, 2019 - 10:59:15 PM

File

Kammerer-Jacquet et al_2019_Me...
Files produced by the author(s)

Identifiers

Citation

S.-F. Kammerer-Jacquet, A. Brunot, M. Lefort, Sahar Bayat, B. Peyronnet, et al.. Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib A Distinct Phenotype Independently Associated With Low PD-L1 Expression. Clinical Genitourinary Cancer, Elsevier, In press, 17 (3), pp.169-176.e1. ⟨10.1016/j.clgc.2019.01.014⟩. ⟨hal-02076598⟩

Share

Metrics

Record views

32

Files downloads

28