Abstract 5426: Genomic and immunohistochemical characterization of patients with advanced papillary renal cell carcinoma: Focus on exceptional responders
Authors: Salgia Nicholas J. , Dizman Nazli , Mambetsariev Isa , Mirzapoiazova Tamara , Zhao Dan , Kulkarni Prakash , Salgia Ravi , Pal Sumanta K. 
Published: September 2020

Background: Approximately 10-15% of patients with renal cell carcinoma (RCC) demonstrate papillary histology. Unfortunately for patients with advanced disease, there is no standard therapy for papillary RCC (pRCC). Herein, we provide detailed biologic characterization of patients with pRCC who have achieved exceptional responses to either targeted therapy or checkpoint inhibition.

Methods: Patients with pRCC were identified from an institutional database. Demographic and treatment-related data were compiled. Genomic characterization using CLIA-certified next-generation sequencing (NGS) platforms (FoundationOne; Foundation Medicine, Cambridge, MA or GEM ExTra: Ashion/TGen, Phoenix, AZ) was performed when deemed clinically relevant; this data was used to characterize the frequency of relevant genomic alterations (GAs) in this subset. Archived tissue was obtained when available and immunohistochemical staining was performed for CD4, CD8, CD11b and other markers to characterize T-cell subtype. Staining for MET, ALK and other protooncogenes was also performed and the spatial relationship between these proteins and immune cells was characterized.

Results: 64 pts with pRCC were identified (50:14 M:F). By International Metastatic RCC Database Consortium (IMDC) criteria, 3 were good risk, 42 were intermediate/poor risk, and 19 were considered unevaluable. Patients received a median of two lines of therapy (range, 1-7). The most common genomic alterations encountered among fifteen patients with available NGS profiling were BAP1 (20%) and TERT (20%). Three patients with ALK mutations were identified – each was treated with FDA approved ALK-inhibitors and all had a response to therapy, with a median progression-free survival (PFS) of 9.65 months (range, 1.25–23.47). Two patients with MET mutations were identified. Fifteen patients received an immune-checkpoint inhibitor as part of their care – eight (53%) experienced a PFS of greater than three months (median PFS, 3.1 months; range, 0.25–43.4). 30 patients received a MET-directed therapy (median PFS, 2.8 months; range, 0.4–29.9), including both patients with recorded MET GAs (PFS of 5.3 and 7.87 months, respectively), and 41 patients received a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor (VEGF-TKI) (median PFS, 4.2 months; range, 0.33–134.47). In total, fifteen patients achieved an exceptional response (&gt;10 months) to therapy. Six such patients also had NGS data and tissue available for immunohistochemical characterization. Immunohistochemical characterization will be reported at the meeting.

Conclusions: Our results indicate that genomic profiling can yield actionable targets in pRCC. Matching these targets to relevant targeted therapies produces clinically meaningful responses.

Citation Format: Nicholas J. Salgia, Nazli Dizman, Isa Mambetsariev, Tamara Mirzapoiazova, Dan Zhao, Prakash Kulkarni, Ravi Salgia, Sumanta K. Pal. Genomic and immunohistochemical characterization of patients with advanced papillary renal cell carcinoma: Focus on exceptional responders [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 5426.