Abstract LB-153: Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study)
Authors: Hirotsugu Uemura, Motohide Uemura, Naoto Sassa, Noboru Nakaigawa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Mototsugu Oya, Nobuo Shinohara, Toyonori Tsuzuki
Journal: Cancer Research (2020)

Abstract Background: The correlation between PD-L1 expression on tumor-infiltrating immune cells and prognosis in renal cell carcinoma (RCC) has been reported in several studies. Methods: A multicenter retrospective study was carried out to investigate the prognostic value of PD-L1 expression (by the VENTANA SP142 immune cell [IC] scoring method) in primary RCC tumors among patients administered systemic therapy for recurrent or metastatic RCC. The primary endpoint was overall survival (OS), defined as the time from the initiation of first-line treatment to the date of death from any cause. The difference in OS between patients of positive PD-L1 status (IC ≥1%) and those of negative status was compared using a stratified log-rank test at a two-sided level of 0.1, stratified by MSKCC risk and liver metastases. Stratified hazard ratio (HR) and its 90% confidence interval (CI) was estimated by the Cox proportional hazard model. An unstratified analysis and an analysis adjusted by propensity score weighting (PSW) were also conducted. Results: We examined 777 RCC surgical specimens, 770 of which were included for primary analysis (7 were excluded owing to indeterminate PD-L1 status). PD-L1 positive was observed in 315 (40.9%). Immune phenotype that describe the level of T-cell presence and activity within the tumor microenvironment differed between PD-L1-positive vs. -negative groups: Excluded (74.3% vs. 31.6%), Inflamed (16.5% vs. 1.5%), and Desert (9.2% vs. 66.8%). PD-L1-positive status was more common in patients with higher clinical stage, higher Fuhrman grade, and presence of sarcomatoid component. A higher proportion of PD-L1-positive patients had poor prognostic features at the start of first-line therapy: 17.5% vs. 7.3% with ‘poor' MSKCC risk; 29.2% vs. 14.9% with ‘poor' IMDC risk. In line with this, fewer PD-L1-positive patients had good prognostic features at the start of first-line therapy: 11.4% vs. 29.7% with ‘favorable' MSKCC risk; 10.8% vs. 26.2% with ‘favorable' IMDC risk.The median OS in PD-L1-positive vs. -negative patients was 30.9 months (95%CI: 25.5-35.7) vs. 37.5 months (95%CI: 34.0-42.6). The stratified HR was 1.04 (90%CI: 0.89-1.22, P=0.65), the unstratified HR was 1.21 (90%CI: 1.04-1.40), and the PSW-adjusted HR was 0.99. Subgroup analysis based on MSKCC risk at the start of first-line therapy revealed that there was no significant difference in mOS based on PD-L1-positive vs. -negative status for ‘favorable' (58.6 vs. 59.8 months; HR: 0.92; 95%CI: 0.54-1.56), ‘intermediate' (31.6 vs. 33.5; HR: 1.06; 95%CI: 0.85-1.32) or ‘poor' (6.6 vs 12.8.; HR: 0.89; 95%CI: 0.55-1.43) categories. Conclusion: This study suggested that PD-L1 status on tumor-infiltrating immune cells was not an independent prognostic factor in recurrent or metastatic RCC patients, although positive PD-L1 status was associated with poor prognostic factors. Citation Format: Hirotsugu Uemura, Motohide Uemura, Naoto Sassa, Noboru Nakaigawa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Mototsugu Oya, Nobuo Shinohara, Toyonori Tsuzuki. Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-153.