The Significance of PARP1 as a biomarker for Predicting the Response to PD-L1 Blockade in Patients with PBRM1-mutated Clear Cell Renal Cell Carcinoma
Menée à partir de données de séquençage de l'ARN de 311 carcinomes rénaux à cellules claires, cette étude met en évidence une association entre le statut de PARP-1 et la réponse aux anti-PD-L1 chez les patients dont la tumeur présente une mutation du gène PBRM1
Immune checkpoint inhibitors (ICIs) have become key agents in the management of clear cell renal cell carcinoma (ccRCC), but their benefits are limited and responders remain unidentified. We investigated the significance of PARP1 in ccRCC using RNA sequencing data for 311 tumors from patients enrolled in prospective clinical trials of PD-1 blockade. Among patients treated with nivolumab (n?=?181), overall survival (OS) was significantly higher in the PARP1-low group than in the PARP1-high group (p?=?0.006), and PARP1 status was significantly associated with OS (hazard ratio [HR] 1.7; p?=?0.007). By contrast, for patients treated with everolimus (n?=?130) there was no significant difference by PARP1 status for progression-free survival (PFS; p?=?0.9) or OS (p?=?0.38). In subgroup analysis for PBRM1-mutated ccRCC, PFS (p?=?0.016) and OS (p?=?0.004) were significantly longer in the group with PARP1-low status and PBRM1 mutation in comparison to the other groups. In addition, PARP1 status was significantly associated with PFS (HR 2.6; p?=?0.007) and OS (HR 3.5; p?=?0.016) among patients with PBRM1-mutated ccRCC treated with nivolumab. Our study suggests that PARP1 can be used as a biomarker for predicting response to ICI treatment for patients with PBRM1-mutated ccRCC.
European Urology , résumé, 2020